Overview

Pathogenicity: Alzheimer's Disease : Pathogenic, Cerebral Amyloid Angiopathy, Down's Syndrome
ACMG/AMP Pathogenicity Criteria: PS1, PS2, PS3, PS4, PM1
Clinical Phenotype Studied: Alzheimer's Disease, Cerebral Amyloid Angiopathy, Down's Syndrome
Coding/Non-Coding: Both
DNA Change: Duplication
Expected RNA Consequence: Duplication
Expected Protein Consequence: Duplication
Genomic Region: Chromosome 21

Findings

The presence of three copies of chromosome 21, which harbors the amyloid precursor protein (APP) gene, is the most common genetic cause of Alzheimer’s disease. Carriers of this alteration have Down syndrome (DS), a condition that results in cognitive disability, alterations in craniofacial morphology, increased risk of congenital heart defects, immune disorders, reduced sense of smell, and a very high risk of developing AD (Antonarakis et al., 2020). Most commonly, trisomy 21 arises because of meiotic nondisjunction in which a pair of chromosomes 21 fail to separate in either the sperm or egg. The frequency of this alteration is relatively high, approximately 0.001 worldwide, according to the World Health Organization. 

Dating back to 1948, multiple studies have shown that middle-aged individuals with DS are likely to develop AD dementia and pathology, including amyloid plaques, neurofibrillary tangles, and neuronal loss (Jervis, 1948; for a review of the history of DSAD see Maure-Blesa et al., 2025). Of note, the original description of amyloid β (Aβ) was in DS (Glenner and Wong, 1984) and contributed to the formulation of the Aβ hypothesis (Lott and Head, 2019). 

Mean age at onset of AD in DS is 54.5 years (Rubenstein et al., 2024), with nearly all individuals with DS developing amyloid plaques by age 40, and more than 95 percent diagnosed with AD dementia by age 70 (Fortea et al., 2021). In a study of more than 130,000 adults with DS in the US, the probability of an incident AD diagnosis over 8 years was 0.63 (95% CI, 0.62-0.64) for those between 55 and 64 years of age when entering the study (Rubenstein et al., 2024). Indeed, AD is currently a leading cause of death in DS adults and may explain their shortened life expectancy (Iulita et al., 2022). Of note, both disease onset and death occurred, on average, later in White non-Hispanics than in Hispanics and Native Americans (Rubenstein et al., 2024). Gender, on the other hand, appears to have minimal effects on disease penetrance, symptom onset, clinical progression, and biomarker trajectories in DSAD, although an interaction between sex and APOE4 has been reported, as well as gender-related effects on transcriptomic profiles (see Del Hoyo Soriano et al., 2025 for review). 

Like AD in the general population, AD in individuals with DS is characterized by dementia and can also be accompanied by gait disturbance, sleep disruption, and seizures. The latter are particularly frequent in DS AD, commonly developing after the third decade of life and before the onset of dementia (Lott and Head, 2019). Behavioral and psychological symptoms of dementia are also observed, particularly during the prodromal stage of disease (Jenkins et al., 2025), and AD-like alterations in the gut microbiome have been reported in a small study of DS individuals with mild cognitive impairment (Rosas et al., 2025).

Overall, AD in DS appears to be the same disease as AD in the general population. Although not identical (Carmona-Iragui et al., 2024), AD biomarker trajectories in DS are very similar to those in autosomal dominant AD and sporadic late onset AD, with very similar links to AD symptomology (Fortea et al., 2020; Hartley et al., 2024; Kac et al., 2024). In addition, as in sporadic and familial AD, APOE4 accelerates the onset of AD in individuals with DS (Bejanin et al., 2021; Jul 2021 news). Also, AD polygenic risk scores were associated with cognitive phenotypes and cerebrospinal fluid (CSF) biomarkers in DS adults, suggesting common pathways influence memory decline in both (Gorijala et al., 2023).  

Interestingly, in the general population, trisomy 21 mosaicism in the brain—affecting only a subpopulation of cells—may contribute to AD and other neurodegenerative diseases (for review see Potter et al., 2016). The effects of mosaicism in individuals with the DS phenotype and trisomy 21 remains uncertain. For example, while one study reported lower plasma Aβ40 and Aβ42 concentrations and lower incidence and prevalence of dementia in mosaic DS individuals compared to non-mosaic DS individuals (Xicota et al., 2024), another found mosaic DS individuals were more susceptible to neurodegenerative conditions, including AD (Rubenstein et al., 2024). 

Neuropathology | Biological Effects | Therapeutics | Research Models

Neuropathology
AD neuropathology in DS surfaces at a young age. Amyloid plaques can start depositing in carriers as early as during the teen years and 20s (e.g., Lemere et al., 1996; Mori et al., 2002), and are seen routinely after age 30. After age 40, when virtually all DS individuals have AD neuropathology, amyloid accumulation ramps up at an exponential rate (Lott and Head, 2019). Moreover, brain metabolism in DS individuals declines with age in a pattern consistent with AD pathology involving temporoparietal regions (e.g., Arriola-Infante et al., 2025) and medial temporal lobe structures progressively shrink (Buehner et al., 2025).

The spread of amyloid and tau pathologies in DSAD generally follows the pattern observed in sporadic AD, as do levels of biomarkers in CSF and blood (e.g., Fortea et al., 2020; Janelidze et al., 2022; July 2022 news; Schworer et al., 2024a; Petersen et al., 2024; Jul 2025 news). Also, the structure of tau fibrils—both paired helical and straight filaments—as well as Aβ42 filaments, appear to be very similar in the two conditions (Fernandez et al., 2024; Ghosh et al., 2024), although two Aβ40 filaments have been identified in DSAD that appear to be distinct from those found in sporadic AD (Fernandez et al., 2024). Moreover, similar amyloid plaque proteomes were identified in DS, early onset AD, and late onset AD (Jul 2025 news; Martá-Ariza et al., 2025). 

However, the progression of AD pathology in DSAD appears to be accelerated. For example, the time from Aβ positivity and tau deposition to initial cognitive decline and dementia was reduced in a study of 167 individuals with DSAD (Schworer et al., 2024b). Consistent with this shortened timeline, amyloid has been reported to accumulate particularly rapidly in DS, with tau neurofibrillary tangles emerging very soon after (Zammit et al., 2024). Also, as revealed by a proteomic analysis of DS cerebrospinal fluid, neuroinflammation, myelin loss, inhibitory interneuron dysfunction, extracellular matrix abnormalities, and blood-brain barrier impairment emerged sooner, and were more pronounced (Montoliu-Gaya et al., 2025; Jul 2025 news). Proteomic analyses of brain tissue were consistent with these findings (Jul 2025 news /news/research-news/downs-syndrome-alzheimers-disease-has-unique-features; Martá-Ariza et al., 2025 /papers/comparison-amyloid-plaque-proteome-down-syndrome-early-onset-alzheimers-disease-and-late-1).

In addition, compared with autosomal dominant AD, tau pathology in DSAD appears to be moderately more widespread, more abundant for a given level of amyloid, and more strongly associated with amyloid accumulation (Wisch et al., 2024). Also, reductions in the thickness of the temporal and parietal cortices, which tracked well with disease stages, were more extensive and severe than those observed in autosomal dominant AD (Kennedy et al., 2025). Comparing levels of plasma glial fibrillary acidic protein (GFAP), a marker of astrogliosis, to markers of amyloid and tau pathologies, one study suggested amyloid may stimulate astrogliosis, which in turn may play a role in fueling tau pathology in the compressed DSAD time course (Boerwinkle et al., 2024). 

Of note, specific brain regions appear to be affected differentially. For example, in DS, PET imaging suggests the striatum is burdened with amyloid very early on and neurofibrillary tangles are particularly dense in DS brains compared with non-DS brains (Lao et al., 2016, Annus et al., 2016, McLachlan et al., 2025). Also, differences in neuropathology in the locus coeruleus, a brain region affected very early in sporadic AD, have been reported. For example, oligomeric tau and Aβ levels were particularly elevated in DSAD compared to late-onset AD in this region (Saternos et al., 2024), while loss of noradrenergic neurons appeared to be less pronounced in DSAD (Fructuoso et al., 2025). Moreover, alongside the development of AD pathology and cognitive decline, the cholinergic system of DS individuals appears to decline more quickly with age than in non-DS individuals (Russell et al., 2025a, Russell et al., 2025b).

Interestingly, the extent of cerebrovascular disease (CVD) in DSAD appears to correlate with the severity of amyloid and tau pathologies, suggesting it is a core feature of DSAD tied to AD progression (Aug 2023 conference news). This characteristic seems to be independent of conventional age-related vascular risk factors, such as hypertension and heart disease, which are less prevalent in DS individuals. A brain imaging study identified enlarged perivascular spaces and infarcts in the early 30s, before global amyloid and tau pathologies reached an inflection point at age 35 (Lao et al., 2024). Microbleeds and white matter hyperintensities surfaced in the 30s and 40s. A detailed study of microbleeds further showed that microbleeds in DS increase with age and AD clinical stage, are more common in APOE4 carriers, and are predominantly found in posterior, lobar brain regions (Zsadanyi et al., 2024). Microbleeds are expected to increase iron levels and, consistent with this, higher levels of iron, iron storage proteins, and lipid peroxidation were observed in DSAD prefrontal cortices compared to control and AD brains (Thorwald et al., 2025).

White matter hyperintensities also increased with age, surfacing 10 years before AD symptom onset with progression closely linked to AD pathology, particularly in periventricular regions, and frontal, parietal, and occipital lobes (Morcillo-Nieto et al., 2024). Also of note, in DS patients who had yet to develop AD, white matter hyperintensities were associated with plasma markers of astrocytosis (GFAP), tau pathology (phospho-tau 217), and neurodegeneration (neurofilament light chain) (Edwards et al., 2024; Rosas et al., 2024). Female gender, lower body mass index, hypertension, and carrying the APOE4 allele were associated with higher levels of cerebrovascular biomarkers for a given age (Lao et al., 2024). 

Individuals with DS appear to have a higher frequency and severity of cerebral amyloid angiopathy (CAA) and have a unique neuroinflammatory phenotype possibly due to serum proteins infiltrating the brain via microbleeds. Indeed, microbleeds correlate with CAA in postmortem cortical tissue from individuals with DS beginning in the mid-30s, mirroring the rise in amyloid plaques (Helman et al., 2019). Also of note, cortical microinfarcts, mostly clustered in the parietal lobes, were found in 12 percent of DS patients and may be tied to a specific ischemic CAA phenotype (Aranha et al., 2024). Despite these pathologies, compared with CAA in carriers of other APP duplications limited to APP with or without a few neighboring genes, CAA in DS appears to be less severe and individuals with DS have a lower frequency of cerebral hematoma (Mann et al., 2018). This may be due to carriers of APP duplications having higher brain levels of total Aβ and shorter Aβ peptides than individuals with DS (Aug 2023 conference news).

DSAD can present with other neurodegenerative pathologies as well. A post-mortem study of 33 DSAD cases, for example, detected Lewy body pathology in the amygdala of 55 percent of individuals between the ages of 41 and 59, and in 75 percent of individuals aged 61 to 72 (Wegiel et al., 2022). In some cases, the distribution of Lewy pathology is atypical (Ichimata et al., 2022). Of note, current methods to measure α-synuclein seeding activity in CSF may fail to detect moderate levels of α-synuclein deposition—a recent study identified seeding activity in only 9 percent of cases, a percentage similar to that reported in autosomal dominant AD and lower than in sporadic AD (Bernhardt et al., 2025). Seeding positivity did not vary with age or clinical status, but plasma neurofilament levels were higher in symptomatic individuals with seeding activity than in those without.

TDP-43 pathology has been reported in 6 to 18 percent of DS patients (e.g., Lippa et al., 2009; Davidson et al., 2011; Ichimata et al., 2022; Wegiel et al., 2022) and hippocampal sclerosis in 6 percent (e.g., Davidson et al., 2011). In one DSAD case, posterior cortical atrophy presented at an early age (Rodríguez-Baz et al., 2024).  

AD and associated neuropathologies have also been reported in individuals with trisomy 21 mosaicism. A man with 10 percent mosaicism in his peripheral lymphocytes, died at age 64 with severe AD neuropathology after being diagnosed with early onset dementia starting at age 55 (Ngo et al., 2024). Pathology included widespread astrogliosis, CAA, perivascular space widening, and Lewy bodies in the amygdala. The extent of mosaicism in the brain was not reported.

An international consortium of brain banks—the Down Syndrome Biobank Consortium—has been established to collect and distribute brain tissue from individuals with DS throughout their lifespan (Aldecoa et al., 2024). It includes 11 sites in Europe, India, and the US.

Biological Effect
APP overexpression and the accumulation of Aβ in the brain is considered the primary driver of dementia in individuals with trisomy 21 (for reviews see Wiseman et al., 2015; Lott and Head, 2019). Consistent with this, at least two individuals with partial trisomy 21, carrying three copies of some parts of chromosome 21 but only two copies of APP, have lived past the age of 70 without developing either dementia or AD pathology (Prasher et al., 1998, Doran et al., 2017). Conversely, families with small chromosome 21 duplications consisting of only a few genes including APP have been reported to suffer from early onset AD. Indeed, there are AD families in which APP is the only gene present within the disease-associated duplication or triplication (APP Duplication 1104 [APP-APP]; see also APP Triplication [APP-APP]). Data from mouse models of DS also support accumulation of Aβ as playing a critical role in DSAD (e.g., Chen et al., 2024; Staurenghi et al., 2024). Of note, increased APP dosage may not only fuel amyloid deposition by increasing Aβ levels, but disrupt other cellular activities, such as endolysosomal function, by hyperactivating RAB5 (Chen et al., 2025a; Chen et al., 2025b).

Consistent with the clinical and genetic findings described above, increasing evidence at the cellular and molecular levels indicate DSAD is mechanistically very similar to AD in the general population. For example, a study that merged spatial transcriptomics and single-nucleus RNA-seq analyses of cortical samples from patients with sporadic AD and DSAD reported broad similarities between the two conditions (Miyoshi et al., 2024; Dec 2024 news), and a transcriptomic analysis of microisolated DSAD cortical neurons revealed alterations predicted to be relevant to sporadic AD (Alldred et al., 2024). Also, a pathway involving the binding of APP β-CTF to a lysosomal proton pump appears to lead to lysosomal dysfunction in both AD and DSAD (Jul 2023 news, Im et al., 2023). 

DSAD may have unique aspects, however, stemming from the overexpression of non-APP genes on chromosome 21, numbering over 200 (see Lott and Head, 2019 for review). For example, increased expression of DYRK1A—which encodes a kinase that phosphorylates many proteins including tau, and splicing factors that modulate tau mRNA splicing resulting in imbalanced 3R-tau and 4R-tau expression—appears to accelerate the emergence of neurofibrillary tangles, along with increased RCAN1, which regulates calcineurin (Dohl et al., 2025). Moreover, DYRK1A phosphoylates tau at threonine 212 (Woods et al., 2001), a modification used as a plasma biomarker of AD due to its strong correlation with AD pathology (Kac et al., 2024). DYRK1A also phosphorylates other AD-related proteins, including glycogen synthase kinase-3β (Skurat and Dietrich, 2004), presenilin 1 (Ryu et al., 2010), and APP (e.g., Ferrer et al., 2005, Ryoo et al., 2008, Garcia-Cerro et al., 2017). Additional DSAD-specific changes have been identified by proteomic and transcriptomic analyses of DSAD brains, including upregulation of ApoE compared with euploid individuals with EOAD or LOAD (Farrell et al., 2025). In this study, APOE expression was elevated in a subset of astrocytes, endothelial cells, and pericytes of the frontal cortex. 

Some genes on chromosome 21 may delay AD pathology. Age at onset for DSAD varies widely, with many individuals suffering from cognitive decline only after age 55, later than the mean age of onset (~52 years) for APP duplication carriers (Wiseman et al., 2015). One study identified a subregion of chromosome 21 that decreases Aβ accumulation in mouse brain (Mumford et al., 2022). This region included BACE2, previously reported as protective against AD pathology (Feb 2020 news, Alić et al., 2021) and, paradoxically, DYRK1A. 

In addition to genetic modifiers of Aβ and tau pathologies, other factors likely modulate the expression of AD in DS individuals. For example, trisomy 21-associated alterations in brain structure, elevated incidence of epilepsy, and disruptions of the immune system that arise during development might increase susceptibility to AD (Lott and Head, 2019). Also, DS-associated mitochondrial dysfunction may accelerate brain aging and AD pathologies (Zuo 2025). Studies of how gene expression is altered in DS brains may reveal additional DS vulnerabilities, such as observed disruptions in RNA splicing that affect cytoskeletal proteins and axonal polarization (Rastogi et al., 2024).

Efforts to identify and understand factors that may confer resistance to AD pathology, as well as resilience to the effects of AD pathology, in DS are underway (see Boyle et al., 2025 for review). For example, a recent report described a woman with DS who remained cognitively stable despite developing AD neuropathology (Liou et al., 2025). Cases like this one could provide insights into AD resilience, or in other cases AD resistance, both in DS and in the general population. Indeed, as described in a preprint, a trisomy 21-linked genetic variant in the microglial-expressed CSF2RB gene was identified as potentially protective against tau pathology, independent of trisomy 21 genetic background (Jin et al., 2024).

Therapeutics
Multiple research groups are investigating methods for detecting DSAD early, monitoring its progression, and assessing the effects of therapeutic interventions. To this end, they are examining the performance of various fluid biomarkers (e.g., Petersen et al., 2024; Wagemann et al., 2025; Zhou et al., 2025; Valle-Tamayo et al., 2025; Kac et al., 2025; Ledreux et al., 2025; Sauer et al., 2025; Janelidze et al., 2025; Varma et al., 2025), cognitive evaluations (e.g., García-Alba et al., 2025; Krinsky-McHale et al., 2025; Ivain et al., 2025; Schworer et al., 2025, Lindner et al., 2025; Soriano et al., 2025), behavioral assessments (e.g., Barry et al., 2025), and brain imaging markers (e.g., Zammit et al., 2025; Mitchell et al., 2025). For example, similar to associations seen in non-DS AD, longitudinal studies of DS adults have shown that elevated plasma levels of phosph-tau217 and glial fibrillary acidic protein (GFAP) predict amyloid buildup, tau pathology, and progression to dementia (Jun 2025 news; Janelidze et al., 2025; Varma et al., 2025).

Of note, longitudinal biomarker studies have been enabled by the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) (Handen et al., 2025) and The Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) (Videla et al., 2025), two groups that have been collecting multimodal biomarker data for over 10 years. 

Several clinical trials to test therapeutics that target amyloid in DS patients are already in the works (see Barroeta et al., 2025 for review). For example, a clinical trial for the anti-amyloid vaccine ACI-24.060a is underway, a trial to evaluate the safety and tolerability of APP antisense oligonucleotides (ASOs) has been registered (NCT06673069), and a trial to test for the anti-Aβ antibody donanemab has been announced (Aug 2024 conference news). Prescribing criteria are being adapted for these patients (e.g., Hillerstrom et al., 2024) and guidelines for amyloid-targeting trials are being developed (Geerts et al., 2024; Krasny et al., 2024). Importantly, these include strategies to mitigate the risk of amyloid-related imaging abnormalities (ARIA) associated with anti-amyloid antibody treatments, a risk which is elevated in individuals with CAA (Aug 2023 conference news) and microbleeds (Zsadanyi et al., 2024), pathologies often found in DS AD. Indeed, a study of postmortem brain tissue from 15 DS patients revealed that the anti-amyloid antibody lecanemab labeled amyloid plaques, indicating potential target engagement, but it also labeled brain blood vessels extensively, indicating a potential safety hazard (Liu et al., 2024). 

Pre-clinical evaluations are also ongoing. For example, γ-secretase modulators have been tested in DS mouse models (Chen et al., 2024). Moreover, the effects of APP and RAB5 ASOs in a DS mouse model (Chen et al., 2025b) and APP ASOs in astrocytes derived from patient induced pluripotent stem cells (Thirumalai et al., 2025) have been examined. 

Research Models
Multiple rodent models of DS have been generated (Herault et al., 2017), with a subset being particularly relevant to AD-DS (Farrell et al., 2022; the following are in the Alzforum Research Models database: Ts65Dn; Dp1Tyb, Dp9Tyb, Dp(16)1Yey/+, TcMAC21). The models have been used for in vivo studies, as well as experiments using cultured cells and organotypic slice cultures. 

Human induced pluripotent stem cells (iPSCs) with trisomy 21 are also available. One research group generated iPSCs from DS individuals with different phenotypes: a 52-year-old with amyloid deposition and an AD diagnosis, and a cognitively unimpaired 51-year-old with no detectable brain amyloid deposition (Clas et al., 2025). Also of note, trisomy 21 iPSCs have been used to create cerebral organoids that model the early pathology of AD (Fertan et al., 2024).

Pathogenicity

Alzheimer's Disease : Pathogenic

This variant fulfilled the following criteria based on the ACMG/AMP guidelines. See a full list of the criteria in the Methods page.

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References

Mutations Citations

1. APOE C130R (ApoE4)
2. APP Duplication 1104 [APP-APP]
3. APP Triplication [APP-APP]

News Citations

1. ApoE4 Hastens Alzheimer’s Disease in Down’s Syndrome 16 Jul 2021
2. In Down's Syndrome, Blood P-Tau217 Detects Plaques and Tangles 8 Jul 2022
3. In Down’s Syndrome, Alzheimer’s Disease Has Unique Features 14 Jul 2025
4. At the Heart of Alzheimer’s in Down’s: Cerebrovascular Disease 25 Aug 2023
5. In Alzheimer’s Due to Down’s, Spatial Omics Spots Signs of Trouble 7 Dec 2024
6. Too Basic: APP β-CTF's YENTPY Motif Binds Proton Pump, Thwarts Lysosomes 26 Jul 2023
7. Can BACE2 Protect Against Amyloidosis? 18 Feb 2020
8. Blood Tests Forecast Dementia in Down’s Syndrome 26 Jun 2025
9. Questions, Questions for Donanemab, Lecanemab 30 Aug 2024

Mutation Position Table Citations

1. APP Duplication - Mutations 8 Mar 2023

Therapeutics Citations

1. ACI-24.060
2. Kisunla
3. Leqembi

Research Models Citations

1. Ts65Dn
2. Dp1Tyb
3. Dp9Tyb
4. Dp(16)1Yey/+
5. TcMAC21

Paper Citations

1. Antonarakis SE, Skotko BG, Rafii MS, Strydom A, Pape SE, Bianchi DW, Sherman SL, Reeves RH. Down syndrome. Nat Rev Dis Primers. 2020 Feb 6;6(1):9. PubMed.
2. JERVIS GA. Early senile dementia in mongoloid idiocy. Am J Psychiatry. 1948 Aug;105(2):102-6. PubMed.
3. Maure-Blesa L, Carmona-Iragui M, Lott I, Head E, Wisniewski T, Rafii MS, Espinosa J, Flórez J, Mobley WC, Holland A, Strydom A, Zaman S, Fortea J. The history of Down syndrome-associated Alzheimer's disease; past, present, and future. Alzheimers Dement. 2025 Jun;21(6):e70158. PubMed.
4. Glenner GG, Wong CW. Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun. 1984 Aug 16;122(3):1131-5. PubMed.
5. Lott IT, Head E. Dementia in Down syndrome: unique insights for Alzheimer disease research. Nat Rev Neurol. 2019 Mar;15(3):135-147. PubMed.
6. Rubenstein E, Tewolde S, Michals A, Weuve J, Fortea J, Fox MP, Pescador Jimenez M, Scott A, Tripodis Y, Skotko BG. Alzheimer Dementia Among Individuals With Down Syndrome. JAMA Netw Open. 2024 Sep 3;7(9):e2435018. PubMed.
7. Fortea J, Zaman SH, Hartley S, Rafii MS, Head E, Carmona-Iragui M. Alzheimer's disease associated with Down syndrome: a genetic form of dementia. Lancet Neurol. 2021 Nov;20(11):930-942. PubMed.
8. Iulita MF, Garzón Chavez D, Klitgaard Christensen M, Valle Tamayo N, Plana-Ripoll O, Rasmussen SA, Roqué Figuls M, Alcolea D, Videla L, Barroeta I, Benejam B, Altuna M, Padilla C, Pegueroles J, Fernandez S, Belbin O, Carmona-Iragui M, Blesa R, Lleó A, Bejanin A, Fortea J. Association of Alzheimer Disease With Life Expectancy in People With Down Syndrome. JAMA Netw Open. 2022 May 2;5(5):e2212910. PubMed.
9. Del Hoyo Soriano L, Wagemann O, Bejanin A, Levin J, Fortea J. Sex-related differences in genetically determined Alzheimer's disease. Front Aging Neurosci. 2025;17:1522434. Epub 2025 Mar 4 PubMed.
10. Jenkins MR, Peven JC, Kubic L, Handen BL, Krinsky-McHale SJ, Hom CL, Lee A, Tudorascu DL, McLachlan M, Zammit M, Minhas D, Luo W, Laymon C, Lee JH, Lott I, Cohen A, Ances BM, Rosas HD, Lai F, Zaman SH, Head E, Mapstone M, Christian BT, Hartley SL, Alzheimer Biomarker Consortium - Down syndrome. Behavioral and psychological symptoms of dementia and Alzheimer's disease progression in Down syndrome. J Neurodev Disord. 2025 Apr 11;17(1):19. PubMed.
11. Rosas HD, Morgan XC, Tao Y, Lai F, Mercaldo ND. Gut dysbiosis in Down syndrome: A potentially unexplored culprit for early Alzheimer's disease. Alzheimers Dement. 2025 Jun;21(6):e70330. PubMed.
12. Carmona-Iragui M, O'Connor A, Llibre-Guerra J, Lao P, Ashton NJ, Fortea J, Sánchez-Valle R. Clinical and research application of fluid biomarkers in autosomal dominant Alzheimer's disease and Down syndrome. EBioMedicine. 2024 Oct;108:105327. Epub 2024 Oct 3 PubMed.
13. Fortea J, Vilaplana E, Carmona-Iragui M, Benejam B, Videla L, Barroeta I, Fernández S, Altuna M, Pegueroles J, Montal V, Valldeneu S, Giménez S, González-Ortiz S, Muñoz L, Estellés T, Illán-Gala I, Belbin O, Camacho V, Wilson LR, Annus T, Osorio RS, Videla S, Lehmann S, Holland AJ, Alcolea D, Clarimón J, Zaman SH, Blesa R, Lleó A. Clinical and biomarker changes of Alzheimer's disease in adults with Down syndrome: a cross-sectional study. Lancet. 2020 Jun 27;395(10242):1988-1997. PubMed.
14. Hartley SL, Handen B, Tudorascu D, Lee L, Cohen A, Schworer EK, Peven JC, Zammit M, Klunk W, Laymon C, Minhas D, Luo W, Zaman S, Ances B, Preboske G, Christian BT, Alzheimer Biomarker Consortium - Down Syndrome. AT(N) biomarker profiles and Alzheimer's disease symptomology in Down syndrome. Alzheimers Dement. 2024 Jan;20(1):366-375. Epub 2023 Aug 28 PubMed.
15. Kac PR, Alcolea D, Montoliu-Gaya L, Fernandez S, LanteroRodriguez J, Maure L, Gonzalez-Ortiz F, Benejam B, Turton M, Barroeta I, Harrison P, Videla L, Ashton NJ, Lleo A, Zetterberg H, Carmona-Iragui M, Karikari TK, Fortea J, Blennow K. Plasma p-tau212 as a biomarker of sporadic and Down Syndrome Alzheimers disease. 2024 Nov 02 10.1101/2024.10.31.24316469 (version 1) medRxiv.
16. Bejanin A, Iulita MF, Vilaplana E, Carmona-Iragui M, Benejam B, Videla L, Barroeta I, Fernandez S, Altuna M, Pegueroles J, Montal V, Valldeneu S, Giménez S, González-Ortiz S, Muñoz L, Padilla C, Aranha MR, Estellés T, Illán-Gala I, Belbin O, Camacho V, Wilson LR, Annus T, Osorio RS, Videla S, Lehmann S, Holland AJ, Zetterberg H, Blennow K, Alcolea D, Clarimon J, Zaman SH, Blesa R, Lleó A, Fortea J. Association of Apolipoprotein E ɛ4 Allele With Clinical and Multimodal Biomarker Changes of Alzheimer Disease in Adults With Down Syndrome. JAMA Neurol. 2021 Aug 1;78(8):937-947. PubMed.
17. Gorijala P, Aslam MM, Dang LT, Xicota L, Fernandez MV, Sung YJ, Fan KH, Feingold E, Surace EI, Chhatwal JP, Hom CL, Dominantly Inherited Alzheimer Network (DIAN), the Alzheimer's Disease Neuroimaging Initiative (ADNI), NIA-LOAD family study, for the Alzheimer's Biomarkers Consortium-Down Syndrome (ABC-DS) Investigators, Hartley SL, Hassenstab J, Perrin RJ, Mapstone M, Zaman SH, Ances BM, Kamboh MI, Lee JH, Cruchaga C. Alzheimer's polygenic risk scores are associated with cognitive phenotypes in Down syndrome. Alzheimers Dement. 2024 Feb;20(2):1038-1049. Epub 2023 Oct 19 PubMed.
18. Potter H, Granic A, Caneus J. Role of Trisomy 21 Mosaicism in Sporadic and Familial Alzheimer's Disease. Curr Alzheimer Res. 2016;13(1):7-17. PubMed.
19. Xicota L, Dang LT, Lee A, Krinsky-McHale S, Pang D, Melilli L, O'Bryant S, Henson RL, Laymon C, Lai F, Rosas HD, Ances B, Lott I, Hom C, Christian B, Hartley S, Zaman S, Head E, Mapstone M, Jin Z, Silverman W, Schupf N, Handen B, Lee JH, Alzheimer's Biomarker Consortium – Down Syndrome (ABC-DS). The effects of mosaicism on biological and clinical markers of Alzheimer's disease in adults with Down syndrome. EBioMedicine. 2024 Dec;110:105433. Epub 2024 Nov 4 PubMed.
20. Rubenstein E, Tewolde S, Skotko BG, Michals A, Fortea J. Occurrence of mosaic Down syndrome and prevalence of co-occurring conditions in Medicaid enrolled adults, 2016-2019. Am J Med Genet C Semin Med Genet. 2024 Dec;196(4):e32097. Epub 2024 Jun 25 PubMed.
21. Lemere CA, Blusztajn JK, Yamaguchi H, Wisniewski T, Saido TC, Selkoe DJ. Sequence of deposition of heterogeneous amyloid beta-peptides and APO E in Down syndrome: implications for initial events in amyloid plaque formation. Neurobiol Dis. 1996 Feb;3(1):16-32. PubMed.
22. Mori C, Spooner ET, Wisniewsk KE, Wisniewski TM, Yamaguch H, Saido TC, Tolan DR, Selkoe DJ, Lemere CA. Intraneuronal Abeta42 accumulation in Down syndrome brain. Amyloid. 2002 Jun;9(2):88-102. PubMed.
23. Arriola-Infante JE, Morcillo-Nieto AO, Zsadanyi SE, Franquesa-Mullerat M, Vaqué-Alcázar L, Rozalem-Aranha M, Arranz J, Rodríguez-Baz Í, Maure-Blesa L, Videla L, Barroeta I, Del Hoyo Soriano L, Benejam B, Fernández S, Sanjuan-Hernández A, Giménez S, Alcolea D, Belbin O, Flotats A, Camacho V, Lleó A, Carmona-Iragui M, Fortea J, Bejanin A. Regional Brain Metabolism across the Alzheimer's Disease Continuum in Down Syndrome. Ann Neurol. 2025 Mar 14; Epub 2025 Mar 14 PubMed.
24. Buehner BJ, Morcillo-Nieto AO, Zsadanyi SE, Rozalem Aranha M, Arriola-Infante JE, Vaqué-Alcázar L, Arranz J, Rodríguez-Baz Í, Maure Blesa L, Videla L, Barroeta I, Del Hoyo Soriano L, Benejam B, Fernández S, Sanjuan Hernandez A, Bargalló N, González-Ortiz S, Giménez S, de Flores R, Yushkevich PA, Alcolea D, Belbin O, Lleó A, Carmona-Iragui M, Fortea J, Bejanin A. Medial temporal lobe atrophy in Down syndrome along the Alzheimer's disease continuum. Brain. 2025 Apr 17; Epub 2025 Apr 17 PubMed.
25. Janelidze S, Christian BT, Price J, Laymon C, Schupf N, Klunk WE, Lott I, Silverman W, Rosas HD, Zaman S, Mapstone M, Lai F, Ances BM, Handen BL, Hansson O. Detection of Brain Tau Pathology in Down Syndrome Using Plasma Biomarkers. JAMA Neurol. 2022 Aug 1;79(8):797-807. PubMed.
26. Schworer EK, Handen BL, Petersen M, O'Bryant S, Peven JC, Tudorascu DL, Lee L, Krinsky-McHale SJ, Hom CL, Clare IC, Christian BT, Schupf N, Lee JH, Head E, Mapstone M, Lott I, Ances BM, Zaman S, Brickman AM, Lai F, Rosas HD, Hartley SL, Alzheimer Biomarker Consortium‐Down Syndrome. Cognitive and functional performance and plasma biomarkers of early Alzheimer's disease in Down syndrome. Alzheimers Dement (Amst). 2024;16(2):e12582. Epub 2024 Apr 14 PubMed.
27. Petersen ME, Flores-Aguilar L, Head E, Montoliu-Gaya L, Strydom A, Pape SE, Fortea J, Ashton NJ, Udeh-Momoh C, O'Bryant SE, German D, Despa F, Mapstone M, Zetterberg H. Blood biomarkers in Down syndrome: Facilitating Alzheimer's disease detection and monitoring. Alzheimers Dement. 2025 Jan;21(1):e14364. Epub 2024 Nov 13 PubMed.
28. Fernandez A, Hoq MR, Hallinan GI, Li D, Bharath SR, Vago FS, Zhang X, Ozcan KA, Newell KL, Garringer HJ, Jiang W, Ghetti B, Vidal R. Cryo-EM structures of amyloid-β and tau filaments in Down syndrome. Nat Struct Mol Biol. 2024 Jun;31(6):903-909. Epub 2024 Mar 29 PubMed.
29. Ghosh U, Tse E, Yang H, Shi M, Caro CD, Wang F, Merz GE, Prusiner SB, Southworth DR, Condello C. Cryo-EM structures reveal tau filaments from Down syndrome adopt Alzheimer's disease fold. Acta Neuropathol Commun. 2024 Jun 12;12(1):94. PubMed.
30. Martá-Ariza M, Leitner DF, Kanshin E, Suazo J, Giusti Pedrosa A, Thierry M, Lee EB, Devinsky O, Drummond E, Fortea J, Lleó A, Ueberheide B, Wisniewski T. Comparison of the amyloid plaque proteome in Down syndrome, early-onset Alzheimer's disease, and late-onset Alzheimer's disease. Acta Neuropathol. 2025 Jan 18;149(1):9. PubMed.
31. Schworer EK, Zammit MD, Wang J, Handen BL, Betthauser T, Laymon CM, Tudorascu DL, Cohen AD, Zaman SH, Ances BM, Mapstone M, Head E, Christian BT, Hartley SL, Alzheimer's Biomarker Consortium–Down Syndrome (ABC–DS). Timeline to symptomatic Alzheimer's disease in people with Down syndrome as assessed by amyloid-PET and tau-PET: a longitudinal cohort study. Lancet Neurol. 2024 Dec;23(12):1214-1224. PubMed.
32. Zammit MD, Betthauser TJ, McVea AK, Laymon CM, Tudorascu DL, Johnson SC, Hartley SL, Converse AK, Minhas DS, Zaman SH, Ances BM, Stone CK, Mathis CA, Cohen AD, Klunk WE, Handen BL, Christian BT, Alzheimer's Biomarker Consortium - Down Syndrome. Characterizing the emergence of amyloid and tau burden in Down syndrome. Alzheimers Dement. 2024 Jan;20(1):388-398. Epub 2023 Aug 29 PubMed.
33. Montoliu-Gaya L, Bian S, Dammer EB, Alcolea D, Sauer M, Martá-Ariza M, Ashton NJ, Belbin O, Fuchs J, Watson CM, Ping L, Duong DM, Nilsson J, Barroeta I, Lantero-Rodriguez J, Videla L, Benejam B, Roberts BR, Blennow K, Seyfried NT, Levey AI, Carmona-Iragui M, Gobom J, Lleó A, Wisniewski T, Zetterberg H, Fortea J, Johnson EC. Proteomic analysis of Down syndrome cerebrospinal fluid compared to late-onset and autosomal dominant Alzheimer´s disease. Nat Commun. 2025 Jul 1;16(1):6003. PubMed.
34. Wisch JK, McKay NS, Boerwinkle AH, Kennedy J, Flores S, Handen BL, Christian BT, Head E, Mapstone M, Rafii MS, O'Bryant SE, Price JC, Laymon CM, Krinsky-McHale SJ, Lai F, Rosas HD, Hartley SL, Zaman S, Lott IT, Tudorascu D, Zammit M, Brickman AM, Lee JH, Bird TD, Cohen A, Chrem P, Daniels A, Chhatwal JP, Cruchaga C, Ibanez L, Jucker M, Karch CM, Day GS, Lee JH, Levin J, Llibre-Guerra J, Li Y, Lopera F, Roh JH, Ringman JM, Supnet-Bell C, van Dyck CH, Xiong C, Wang G, Morris JC, McDade E, Bateman RJ, Benzinger TL, Gordon BA, Ances BM, Alzheimer's Biomarker Consortium-Down syndrome, Dominantly Inherited Alzheimer Network. Comparison of tau spread in people with Down syndrome versus autosomal-dominant Alzheimer's disease: a cross-sectional study. Lancet Neurol. 2024 May;23(5):500-510. PubMed.
35. Kennedy JT, Wisch JK, Dincer A, Roman J, Gordon BA, Handen B, Benzinger TL, Head E, Mapstone M, Christian BT, Tudorascu DL, Laymon CL, Hartley SL, Lao P, Brickman AM, Zaman SH, Ances BM, ABC‐DS and DIAN Consortia. Decoding brain structure to stage Alzheimer's disease pathology in Down syndrome. Alzheimers Dement. 2025 Feb;21(2):e14519. Epub 2025 Jan 14 PubMed.
36. Boerwinkle AH, Wisch JK, Handen BL, Head E, Mapstone M, Rafii MS, O'Bryant SE, Krinsky-McHale SJ, Lai F, Rosas HD, Zaman S, Lott IT, Tudorascu D, Zammit M, Brickman AM, Lee JH, Ances BM, Alzheimer's Biomarker Consortium‐Down Syndrome. The mediating role of plasma glial fibrillary acidic protein in amyloid and tau pathology in Down's syndrome. Alzheimers Dement. 2025 Jan;21(1):e14359. Epub 2024 Nov 13 PubMed.
37. Lao PJ, Betthauser TJ, Hillmer AT, Price JC, Klunk WE, Mihaila I, Higgins AT, Bulova PD, Hartley SL, Hardison R, Tumuluru RV, Murali D, Mathis CA, Cohen AD, Barnhart TE, Devenny DA, Mailick MR, Johnson SC, Handen BL, Christian BT. The effects of normal aging on amyloid-β deposition in nondemented adults with Down syndrome as imaged by carbon 11-labeled Pittsburgh compound B. Alzheimers Dement. 2016 Apr;12(4):380-90. Epub 2015 Jun 13 PubMed.
38. Annus T, Wilson LR, Hong YT, Acosta-Cabronero J, Fryer TD, Cardenas-Blanco A, Smith R, Boros I, Coles JP, Aigbirhio FI, Menon DK, Zaman SH, Nestor PJ, Holland AJ. The pattern of amyloid accumulation in the brains of adults with Down syndrome. Alzheimers Dement. 2016 May;12(5):538-45. Epub 2015 Sep 9 PubMed.
39. McLachlan M, Bettcher B, McVea A, DiFilippo A, Zammit M, LeMerise L, Rouanet J, Price J, Tudorascu D, Laymon C, Keator D, Lao P, Brickman AM, Fryer T, Hartley S, Ances BM, Rosas HD, Johnson S, Betthauser T, Stone CK, Zaman S, Handen B, Head E, Mapstone M, Christian BT, Investigators AD. The striatum is an early, accurate indicator of amyloid burden using [11C]PiB in Down syndrome: Comparison of two radiotracers. Alzheimers Dement. 2025 Apr;21(4):e70141. PubMed.
40. Saternos H, Hamlett ED, Guzman S, Head E, Granholm AC, Ledreux A. Unique Pathology in the Locus Coeruleus of Individuals with Down Syndrome. J Alzheimers Dis. 2024;101(2):541-561. PubMed.
41. Fructuoso M, Vermeiren Y, Boluda S, Stimmer L, Crans RA, Xicota L, Eisel U, Casan NO, Bun P, Duyckaerts C, Delabar JM, Strydom A, Van Dam D, Dierssen M, De Deyn P, Potier MC. Disease-specific neuropathological alterations of the locus coeruleus in Alzheimer's disease, Down syndrome, and Parkinson's disease. Alzheimers Dement. 2025 Jun;21(6):e70262. PubMed.
42. Russell JK, Conley AC, Boyd BD, Begnoche JP, Schlossberg R, Stranick A, Rosenberg AJ, Acosta LM, Martin D, Neal Y, Kanel P, Albin RL, Rafii MS, Dumas J, Newhouse PA. Differences in cholinergic terminal density in adults with Down syndrome compared to neurotypical controls measured by [18F]-fluoroethoxybenzovesamicol positron emission tomography imaging. Neurobiol Aging. 2025 Apr;148:50-60. Epub 2025 Jan 30 PubMed.
43. Russell JK, Conley AC, Boyd BD, Begnoche JP, Schlossberg R, Stranick A, Rosenberg AJ, Acosta LM, Martin D, Neal Y, Rafii MS, Dumas J, Newhouse PA. Brain cholinergic terminal density utilizing [18F]-fluoroethoxybenzovesamicol PET in adults with Down's syndrome: Relationship to amyloid PET and cognitive performance. Alzheimers Dement. 2025 Apr;21(4):e70134. PubMed.
44. Lao P, Edwards N, Flores-Aguilar L, Alshikho M, Rizvi B, Tudorascu D, Rosas HD, Yassa M, Christian BT, Mapstone M, Handen B, Zimmerman ME, Gutierrez J, Wilcock D, Head E, Brickman AM. Cerebrovascular disease emerges with age and Alzheimer's disease in adults with Down syndrome. Sci Rep. 2024 May 29;14(1):12334. PubMed.
45. Zsadanyi SE, Morcillo-Nieto AO, Aranha MR, Aragón I, Arriola-Infante JE, Vaqué-Alcázar L, Montal V, Pegueroles J, Arranz J, Rodríguez-Baz Í, Blesa LM, Videla L, Barroeta I, Del Hoyo Soriano L, Benejam B, Fernández S, Hernandez AS, Bargallo N, González-Ortiz S, Giménez S, Alcolea D, Belbin O, Lleó A, Fortea J, Carmona-Iragui M, Bejanin A. Associations of Microbleeds and Their Topography With Imaging and CSF Biomarkers of Alzheimer Pathology in Individuals With Down Syndrome. Neurology. 2024 Aug 27;103(4):e209676. Epub 2024 Jul 29 PubMed.
46. Thorwald MA, Godoy-Lugo JA, Kerstiens E, Garcia G, Kim M, Shemtov SJ, Silva J, Durra S, O'Day PA, Mack WJ, Hiniker A, Vermulst M, Benayoun BA, Higuchi-Sanabria R, Forman HJ, Head E, Finch CE. Down syndrome with Alzheimer's disease brains have increased iron and associated lipid peroxidation consistent with ferroptosis. Alzheimers Dement. 2025 Jun;21(6):e70322. PubMed.
47. Morcillo-Nieto AO, Zsadanyi SE, Arriola-Infante JE, Carmona-Iragui M, Montal V, Pegueroles J, Aranha MR, Vaqué-Alcázar L, Padilla C, Benejam B, Videla L, Barroeta I, Fernandez S, Altuna M, Giménez S, González-Ortiz S, Bargalló N, Ribas L, Arranz J, Torres S, Iulita MF, Belbin O, Camacho V, Alcolea D, Lleó A, Fortea J, Bejanin A. Characterization of white matter hyperintensities in Down syndrome. Alzheimers Dement. 2024 Sep;20(9):6527-6541. Epub 2024 Aug 1 PubMed.
48. Edwards NC, Lao PJ, Alshikho MJ, Ericsson OM, Rizvi B, Petersen ME, O'Bryant S, Aguilar LF, Simoes S, Mapstone M, Tudorascu DL, Janelidze S, Hansson O, Handen BL, Christian BT, Lee JH, Lai F, Rosas HD, Zaman S, Lott IT, Yassa MA, Alzheimer’s Biomarkers Consortium–Down Syndrome (ABC-DS) Investigators, Gutierrez J, Wilcock DM, Head E, Brickman AM. Cerebrovascular disease is associated with Alzheimer's plasma biomarker concentrations in adults with Down syndrome. Brain Commun. 2024;6(5):fcae331. Epub 2024 Sep 25 PubMed.
49. Rosas HD, Mercaldo ND, Hasimoglu Y, Petersen M, Lewis LR, Lai F, Powell D, Dhungana A, Demir A, Keater D, Yassa M, Brickman AM, O'Bryant S. Association of plasma neurofilament light chain with microstructural white matter changes in Down syndrome. Alzheimers Dement (Amst). 2024;16(4):e70023. Epub 2024 Nov 22 PubMed.
50. Helman AM, Siever M, McCarty KL, Lott IT, Doran E, Abner EL, Schmitt FA, Head E. Microbleeds and Cerebral Amyloid Angiopathy in the Brains of People with Down Syndrome with Alzheimer's Disease. J Alzheimers Dis. 2019;67(1):103-112. PubMed.
51. Aranha MR, Montal V, van den Brink H, Pegueroles J, Carmona-Iragui M, Videla L, Maure Blesa L, Benejam B, Arranz J, Valldeneu S, Barroeta I, Fernández S, Ribas L, Alcolea D, González-Ortiz S, Bargalló N, Biessels GJ, Blesa R, Lleó A, Coutinho AM, Leite CC, Bejanin A, Fortea J. Cortical microinfarcts in adults with Down syndrome assessed with 3T-MRI. Alzheimers Dement. 2024 Jun;20(6):3906-3917. Epub 2024 Apr 21 PubMed.
52. Mann DM, Davidson YS, Robinson AC, Allen N, Hashimoto T, Richardson A, Jones M, Snowden JS, Pendleton N, Potier MC, Laquerrière A, Prasher V, Iwatsubo T, Strydom A. Patterns and severity of vascular amyloid in Alzheimer's disease associated with duplications and missense mutations in APP gene, Down syndrome and sporadic Alzheimer's disease. Acta Neuropathol. 2018 Oct;136(4):569-587. Epub 2018 May 16 PubMed.
53. Wegiel J, Flory M, Kuchna I, Nowicki K, Wegiel J, Ma SY, Zhong N, Bobrowicz TW, de Leon M, Lai F, Silverman WP, Wisniewski T. Developmental deficits and staging of dynamics of age associated Alzheimer's disease neurodegeneration and neuronal loss in subjects with Down syndrome. Acta Neuropathol Commun. 2022 Jan 4;10(1):2. PubMed.
54. Ichimata S, Yoshida K, Visanji NP, Lang AE, Nishida N, Kovacs GG. Patterns of Mixed Pathologies in Down Syndrome. J Alzheimers Dis. 2022;87(2):595-607. PubMed.
55. Bernhardt AM, Rodríguez-Baz Í, Aldecoa I, Arranz J, Arriola-Infante JE, Maure-Blesa L, Carmona-Iragui M, Longen S, Trossbach SV, Giese A, Matthias T, Benejam B, Videla L, Del Hoyo Soriano L, Barroeta I, Sanjuan A, Fernández S, Vaqué-Alcázar L, Rozalem Aranha M, Morcillo-Nieto AO, Nübling G, Wagemann O, Stockbauer A, Tondo M, Bejanin A, Lleó A, Alcolea D, Molina-Porcel L, Fortea J, Levin J. Alpha-synuclein co-pathology in Down syndrome-associated Alzheimer's disease. Alzheimers Dement. 2025 Jun;21(6):e70342. PubMed.
56. Lippa CF, Rosso AL, Stutzbach LD, Neumann M, Lee VM, Trojanowski JQ. Transactive response DNA-binding protein 43 burden in familial Alzheimer disease and Down syndrome. Arch Neurol. 2009 Dec;66(12):1483-8. PubMed.
57. Davidson YS, Raby S, Foulds PG, Robinson A, Thompson JC, Sikkink S, Yusuf I, Amin H, DuPlessis D, Troakes C, Al-Sarraj S, Sloan C, Esiri MM, Prasher VP, Allsop D, Neary D, Pickering-Brown SM, Snowden JS, Mann DM. TDP-43 pathological changes in early onset familial and sporadic Alzheimer's disease, late onset Alzheimer's disease and Down's syndrome: association with age, hippocampal sclerosis and clinical phenotype. Acta Neuropathol. 2011 Dec;122(6):703-13. Epub 2011 Oct 4 PubMed.
58. Rodríguez-Baz Í, Benejam B, Morcillo-Nieto AO, Vaqué-Alcázar L, Arriola-Infante JE, Camacho V, Aranha MR, Carmona-Iragui M, Videla L, Barroeta I, Fernández S, Zsadanyi SE, Giménez S, Arranz J, Maure Blesa L, Alcolea D, Lleó A, Bejanin A, Fortea J. Posterior Cortical Atrophy Due to Alzheimer Disease in a Person With Down Syndrome: A Case Report. Neurology. 2025 Jan 14;104(1):e210179. Epub 2024 Dec 17 PubMed.
59. Ngo PT, Pascual JR, Wright S, Williams CK, Magaki S, Yong WH, Vinters HV, Ringman JM, Head E. Neuropathology of trisomy 21 mosaicism in a case with early-onset dementia. Alzheimers Dement. 2025 Jan;21(1):e14394. Epub 2024 Dec 10 PubMed.
60. Aldecoa I, Barroeta I, Carroll SL, Fortea J, Gilmore A, Ginsberg SD, Guzman SJ, Hamlett ED, Head E, Perez SE, Potter H, Molina-Porcel L, Raha-Chowdhury R, Wisniewski T, Yong WH, Zaman S, Ghosh S, Mufson EJ, Granholm AC. Down Syndrome Biobank Consortium: A perspective. Alzheimers Dement. 2024 Mar;20(3):2262-2272. Epub 2024 Jan 25 PubMed.
61. Wiseman FK, Al-Janabi T, Hardy J, Karmiloff-Smith A, Nizetic D, Tybulewicz VL, Fisher EM, Strydom A. A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome. Nat Rev Neurosci. 2015 Sep;16(9):564-74. Epub 2015 Aug 5 PubMed.
62. Prasher VP, Farrer MJ, Kessling AM, Fisher EM, West RJ, Barber PC, Butler AC. Molecular mapping of Alzheimer-type dementia in Down's syndrome. Ann Neurol. 1998 Mar;43(3):380-3. PubMed.
63. Doran E, Keator D, Head E, Phelan MJ, Kim R, Totoiu M, Barrio JR, Small GW, Potkin SG, Lott IT. Down Syndrome, Partial Trisomy 21, and Absence of Alzheimer's Disease: The Role of APP. J Alzheimers Dis. 2017;56(2):459-470. PubMed.
64. Chen XQ, Becker A, Albay R, Nguyen PD, Karachentsev D, Roberts AJ, Rynearson KD, Tanzi RE, Mobley WC. γ-Secretase Modulator BPN15606 Reduced Aβ42 and Aβ40 and Countered Alzheimer-Related Pathologies in a Mouse Model of Down Syndrome. Ann Neurol. 2024 Aug;96(2):390-404. Epub 2024 May 15 PubMed.
65. Staurenghi E, Testa G, Leoni V, Cecci R, Floro L, Giannelli S, Barone E, Perluigi M, Leonarduzzi G, Sottero B, Gamba P. Altered Brain Cholesterol Machinery in a Down Syndrome Mouse Model: A Possible Common Feature with Alzheimer's Disease. Antioxidants (Basel). 2024 Apr 3;13(4) PubMed.
66. Chen XQ, Zuo X, Becker A, Mobley WC. Hyperactivation of RAB5 disrupts the endosomal Rab cascade leading to endolysosomal dysregulation in Down syndrome: A necessary role for increased APP gene dose. Alzheimers Dement. 2025 May;21(5):e70046. PubMed.
67. Chen XQ, Zuo X, Becker A, Mante M, Florio JB, Jadhav SG, Albay R, Johnstone A, Karachentsev D, Rissman R, Zhao H, Dowdy SF, Mobley WC. Antisense oligonucleotides directed against App and Rab5 normalized endosomal Rab activity and reversed DS-AD-linked degenerative phenotypes in the Dp16 mouse model of Down syndrome. Alzheimers Dement. 2025 May;21(5):e70022. PubMed.
68. Miyoshi E, Morabito S, Henningfield CM, Das S, Rahimzadeh N, Shabestari SK, Michael N, Emerson N, Reese F, Shi Z, Cao Z, Srinivasan SS, Scarfone VM, Arreola MA, Lu J, Wright S, Silva J, Leavy K, Lott IT, Doran E, Yong WH, Shahin S, Perez-Rosendahl M, Alzheimer’s Biomarkers Consortium–Down Syndrome (ABC–DS), Head E, Green KN, Swarup V. Spatial and single-nucleus transcriptomic analysis of genetic and sporadic forms of Alzheimer's disease. Nat Genet. 2024 Dec;56(12):2704-2717. Epub 2024 Nov 22 PubMed.
69. Alldred MJ, Pidikiti H, Ibrahim KW, Lee SH, Heguy A, Hoffman GE, Roussos P, Wisniewski T, Wegiel J, Stutzmann GE, Mufson EJ, Ginsberg SD. Analysis of microisolated frontal cortex excitatory layer III and V pyramidal neurons reveals a neurodegenerative phenotype in individuals with Down syndrome. Acta Neuropathol. 2024 Aug 6;148(1):16. PubMed.
70. Im E, Jiang Y, Stavrides PH, Darji S, Erdjument-Bromage H, Neubert TA, Choi JY, Wegiel J, Lee JH, Nixon RA. Lysosomal dysfunction in Down syndrome and Alzheimer mouse models is caused by v-ATPase inhibition by Tyr682-phosphorylated APP βCTF. Sci Adv. 2023 Jul 28;9(30):eadg1925. Epub 2023 Jul 26 PubMed.
71. Dohl J, Treadwell Z, Norris C, Head E. Calcineurin inhibition may prevent Alzheimer disease in people with Down syndrome. Alzheimers Dement. 2025 Mar;21(3):e70034. PubMed.
72. Woods YL, Cohen P, Becker W, Jakes R, Goedert M, Wang X, Proud CG. The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bepsilon at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase. Biochem J. 2001 May 1;355(Pt 3):609-15. PubMed.
73. Kac PR, González-Ortiz F, Emeršič A, Dulewicz M, Koutarapu S, Turton M, An Y, Smirnov D, Kulczyńska-Przybik A, Varma VR, Ashton NJ, Montoliu-Gaya L, Camporesi E, Winkel I, Paradowski B, Moghekar A, Troncoso JC, Lashley T, Brinkmalm G, Resnick SM, Mroczko B, Kvartsberg H, Gregorič Kramberger M, Hanrieder J, Čučnik S, Harrison P, Zetterberg H, Lewczuk P, Thambisetty M, Rot U, Galasko D, Blennow K, Karikari TK. Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer's disease neuropathology. Nat Commun. 2024 Mar 23;15(1):2615. PubMed.
74. Skurat AV, Dietrich AD. Phosphorylation of Ser640 in muscle glycogen synthase by DYRK family protein kinases. J Biol Chem. 2004 Jan 23;279(4):2490-8. Epub 2003 Oct 30 PubMed.
75. Ryu YS, Park SY, Jung MS, Yoon SH, Kwen MY, Lee SY, Choi SH, Radnaabazar C, Kim MK, Kim H, Kim K, Song WJ, Chung SH. Dyrk1A-mediated phosphorylation of Presenilin 1: a functional link between Down syndrome and Alzheimer's disease. J Neurochem. 2010 Nov;115(3):574-84. Epub 2010 Aug 19 PubMed.
76. Ferrer I, Barrachina M, Puig B, Martínez de Lagrán M, Martí E, Avila J, Dierssen M. Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Neurobiol Dis. 2005 Nov;20(2):392-400. PubMed.
77. Ryoo SR, Cho HJ, Lee HW, Jeong HK, Radnaabazar C, Kim YS, Kim MJ, Son MY, Seo H, Chung SH, Song WJ. Dual-specificity tyrosine(Y)-phosphorylation regulated kinase 1A-mediated phosphorylation of amyloid precursor protein: evidence for a functional link between Down syndrome and Alzheimer's disease. J Neurochem. 2008 Mar;104(5):1333-44. Epub 2007 Nov 14 PubMed.
78. García-Cerro S, Rueda N, Vidal V, Lantigua S, Martínez-Cué C. Normalizing the gene dosage of Dyrk1A in a mouse model of Down syndrome rescues several Alzheimer's disease phenotypes. Neurobiol Dis. 2017 Oct;106:76-88. Epub 2017 Jun 21 PubMed.
79. Farrell C, Buhidma Y, Mumford P, Heywood WE, Hällqvist J, Flores-Aguilar L, Andrews EJ, Rahimzadah N, Taso OS, Doran E, Swarup V, Head E, Lashley T, Mills K, Toomey CE, Wiseman FK. Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome-Alzheimer's disease. Acta Neuropathol. 2025 May 19;149(1):49. PubMed.
80. Mumford P, Tosh J, Anderle S, Gkanatsiou Wikberg E, Lau G, Noy S, Cleverley K, Saito T, Saido TC, Yu E, Brinkmalm G, Portelius E, Blennow K, Zetterberg H, Tybulewicz V, Fisher EM, Wiseman FK. Genetic Mapping of APP and Amyloid-β Biology Modulation by Trisomy 21. J Neurosci. 2022 Aug 17;42(33):6453-6468. Epub 2022 Jul 14 PubMed.
81. Alić I, Goh PA, Murray A, Portelius E, Gkanatsiou E, Gough G, Mok KY, Koschut D, Brunmeir R, Yeap YJ, O'Brien NL, Groet J, Shao X, Havlicek S, Dunn NR, Kvartsberg H, Brinkmalm G, Hithersay R, Startin C, Hamburg S, Phillips M, Pervushin K, Turmaine M, Wallon D, Rovelet-Lecrux A, Soininen H, Volpi E, Martin JE, Foo JN, Becker DL, Rostagno A, Ghiso J, Krsnik Ž, Šimić G, Kostović I, Mitrečić D, LonDownS Consortium, Francis PT, Blennow K, Strydom A, Hardy J, Zetterberg H, Nižetić D. Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain. Mol Psychiatry. 2021 Oct;26(10):5766-5788. Epub 2020 Jul 10 PubMed. bioRxiv.
82. Zuo X. Mitochondrial Imbalance in Down Syndrome: A Driver of Accelerated Brain Aging?. Aging Dis. 2025 Apr 6;16(5):2674-2694. PubMed.
83. Rastogi M, Bartolucci M, Nanni M, Aloisio M, Vozzi D, Petretto A, Contestabile A, Cancedda L. Integrative multi-omic analysis reveals conserved cell-projection deficits in human Down syndrome brains. Neuron. 2024 May 21; PubMed.
84. Boyle R, Koops EA, Ances B, Andrews EJ, Arenaza-Urquijo EM, Benjanin A, Brickman AM, Buckley RF, Clas GS, Costello E, Coughlan GT, Conley AC, Deng F, de Paula Faria D, Edwards N, Flores-Aguilar L, Fortea J, Ghazi Saidi L, Head E, Hom CL, Koenig K, Lao P, Lengyel I, Li YJ, Loi S, Loughrey D, McGlinchey E, Newhouse P, Pertierra L, Prokopiou PC, Qi Q, de Paula França Resende E, Russell J, Scanlon CE, Schneider C, Schultz SA, Seto M, Shaka S, Soldan A, Vaqué Alcázar L, Weng Y, Wilson JE, Zaman SH, Zsadányi SE, Hartley S. Resistance and resilience to Alzheimer's disease in Down syndrome. Alzheimers Dement. 2025 Apr;21(4):e70151. PubMed.
85. Liou JJ, Lou J, Flores-Aguilar L, Nakagiri J, Yong W, Hom CL, Doran EW, Totoiu MO, Lott I, Mapstone M, Keator DB, Brickman AM, Wright ST, Nelson B, Lai F, Xicota L, Dang LT, Li J, Santini T, Mettenburg JM, Ikonomovic MD, Kofler J, Ibrahim T, Head E, Alzheimer Biomarker Consortium ‐ Down Syndrome. A neuropathology case report of a woman with Down syndrome who remained cognitively stable: Implications for resilience to neuropathology. Alzheimers Dement. 2025 Feb;21(2):e14479. Epub 2025 Jan 27 PubMed.
86. Wagemann O, Nübling G, Martínez-Murcia FJ, Wlasich E, Loosli SV, Sandkühler K, Stockbauer A, Prix C, Katzdobler S, Petrera A, Hauck SM, Fortea J, Romero-Zaliz R, Jiménez-Mesa C, Górriz Sáez JM, Höglinger G, Levin J. Exploratory analysis of the proteomic profile in plasma in adults with Down syndrome in the context of Alzheimer's disease. Alzheimers Dement. 2025 Mar;21(3):e70040. PubMed.
87. Zhou Y, Sheehan R, Guo L, Strydom A. Blood-based biomarkers for Alzheimer's disease in Down syndrome: A systematic review and meta-analysis. Alzheimers Dement. 2025 Apr;21(4):e70135. PubMed.
88. Valle-Tamayo N, Aranha MR, Pérez-González R, Serrano-Requena S, Videla L, Barroeta I, Benejam B, Chiva-Blanch G, Jimenez A, Busciglio J, Wisniewski T, Carmo SD, Álvarez-Sánchez E, Muñoz L, Bejanin A, Belbin O, Alcolea D, Carmona-Iragui M, Lleó A, Cuello AC, Fortea J, Dols-Icardo O, Iulita MF. Nerve growth factor precursor alterations in neuron-derived extracellular vesicles from individuals with Down syndrome along the Alzheimer's disease continuum. Alzheimers Dement. 2025 Apr;21(4):e70137. PubMed.
89. Kac PR, Alcolea D, Montoliu-Gaya L, Fernández S, Rodriguez JL, Maure L, González-Ortiz F, Benejam B, Turton M, Barroeta I, Harrison P, Videla L, Ashton NJ, Lleó A, Zetterberg H, Carmona-Iragui M, Karikari TK, Fortea J, Blennow K. Plasma p-tau212 as a biomarker of sporadic and Down syndrome Alzheimer's disease. Alzheimers Dement. 2025 Apr;21(4):e70172. PubMed.
90. Ledreux A, Carmona-Iragui M, Videla L, Benejam B, Barroeta I, Lleó A, Alcolea D, Fortea J. Cargo of small extracellular vesicles from neuronal origin shows progression of dementia in individuals with Down syndrome. Alzheimers Dement. 2025 Jun;21(6):e70380. PubMed.
91. Sauer M, Gomes BF, Shahrouki P, Lantero-Rodriguez J, Montoliu-Gaya L, Camporesi E, Belbin O, Alcolea D, Kumar A, Sharma M, Singh S, Brinkmalm G, Gobom J, Carmona-Iragui M, Schöll M, Janelidze S, Deep G, Blennow K, Zetterberg H, Brinkmalm A, Lleó A, Fortea J, Hansson O, Ashton NJ, Nilsson J. Development and validation of a novel Simoa assay for NPTX2 in Alzheimer's disease and Down syndrome. Alzheimers Dement. 2025 Jun;21(6):e70241. PubMed.
92. Janelidze S, Collij LE, Mattsson-Carlgren N, Antill A, Laymon CM, Lott I, Rosas HD, Minhas DS, Luo W, Zaman S, Alzheimer's Biomarker Consortium–Down Syndrome investigators, Mapstone M, Head E, Lai F, Hartley SL, Ances BM, Krinsky-McHale SJ, Lee JH, Ossenkoppele R, Christian BT, Handen BL, Hansson O. Prediction of amyloid and tau brain deposition and cognitive decline in people with Down syndrome using plasma biomarkers: a longitudinal cohort study. Lancet Neurol. 2025 Jul;24(7):591-600. PubMed.
93. Varma VR, An Y, Kac PR, Bilgel M, Moghekar A, Loeffler T, Amschl D, Daurer M, Prokesch M, Troncoso J, Blennow K, Zetterberg H, Ashton NJ, Ferrucci L, Resnick SM, Thambisetty M. Longitudinal progression of blood biomarkers reveals a key role of reactive astrocytosis in preclinical Alzheimer's disease. Med. 2025 Sep 12;6(9):100724. Epub 2025 Jun 9 PubMed.
94. García-Alba J, Molanes-López EM, Zuluaga P, Bell-Fenellos C, Vaquero L, Alfayate E, García F, Mateo G, Modenhauer F, Galván-Román JM, Bajo R, Fernández A. Cognitive markers for the distinction between asymptomatic and prodromal Alzheimer's disease in Down syndrome: Correlations with volumetric brain changes. Alzheimers Dement (Amst). 2025;17(1):e70084. Epub 2025 Feb 11 PubMed.
95. Krinsky-McHale SJ, Kovacs CM, Lee JH, Listwan TA, Pang DI, Schupf N, Tycko B, Zigman WB, Silverman W. Validity of one-time assessments for identifying prodromal Alzheimer's disease in adults with Down syndrome. Alzheimers Dement (Amst). 2025;17(1):e70076. Epub 2025 Feb 11 PubMed.
96. Ivain P, Baksh A, Saini F, Idris M, Tamayo-Elizalde M, Wells J, Benejam B, Loosli SV, Sandkühler K, Wlasich E, Wagemann O, Levin J, Martet D, Sacco S, Falquero S, Clert M, Rebillat AS, Khoo WM, Smith MA, Beresford-Webb J, Zaman S, Carmona-Iragui M, Videla L, Fortea J, Langballe EM, Medbøen IT, Larsen FK, Baldimtsi E, Paradisi R, Ntailakis P, Tsolaki M, Papantoniou G, McGlinchey E, McCarron M, Kennelly S, Strydom A. Validation of the CAMCOG-DS-II, a neuropsychological test battery for Alzheimer's disease in people with Down syndrome: A Horizon 21 European Down syndrome Consortium study. Alzheimers Dement. 2025 Mar;21(3):e70071. PubMed.
97. Schworer EK, Handen BL, Krinsky-McHale S, Hom CL, Clare IC, Harp JP, Pulsifer MB, Mapstone M, Head E, Christian BT, Hartley SL, Alzheimer Biomarker Consortium‐Down Syndrome. Modified Cued Recall Test: Longitudinal Analysis of Test Versions and Item Recall in Adults With Down Syndrome. J Intellect Disabil Res. 2025 Jul;69(7):569-581. Epub 2025 Apr 20 PubMed.
98. Lindner H, Merabet LB, Lundqvist LO. The feasibility of using eye-tracking technology for cognitive screening in Down syndrome with dementia: A cross-sectional case series. Alzheimers Dement. 2025 Jun;21(6):e70385. PubMed.
99. Soriano LD, Sandkühler K, Videla L, Benejam B, Carmona-Iragui M, Wlasich E, Kustermann J, Barroeta I, Vaqué-Alcázar L, Rodríguez-Baz Í, Bejanin A, Fernández S, Arranz J, Arriola-Infante JE, Maure-Blesa L, Juan AS, Nübling G, Wagemann O, Stockbauer A, Hassenstab J, Levin J, Fortea J. Discrepancies in assessing intellectual disability levels in adults with Down syndrome: Implications for dementia diagnosis. Alzheimers Dement. 2025 Jun;21(6):e70307. PubMed.
100. Barry A, Peven JC, Handen BL, Bolt D, Krinsky-McHale SJ, Hom CL, Clare IC, Glueck A, Harp J, Schmitt F, Zammit M, Minhas D, Luo W, Laymon C, Price J, Lee JH, Lott I, Cohen A, Ances BM, Pulsifer M, Rosa HD, Lai F, Zaman SH, Head E, Mapstone M, Christian BT, Hartley SL, Alzheimer Biomarker Consortium ‐ Down syndrome. Longitudinal investigation of gait and Alzheimer's disease in adults with Down syndrome. Alzheimers Dement. 2025 Apr;21(4):e70211. PubMed.
101. Zammit MD, Price JC, Christian BT, Rafii MS. A head-to-head comparison of multiple amyloid PET radiotracers for Down syndrome clinical trials. 2025 Mar 19 10.1101/2025.03.18.25324200 (version 1) medRxiv.
102. Mitchell J, Threlfall A, Sloan K, Smyth L, Beresford-Webb J, Walpert MJ, Peto T, MacGillivray T, Holland A, Lengyel I, Csincsik L. Choroidal and retinal vascular changes in adults with Down syndrome: Insights into the Alzheimer's disease continuum. Alzheimers Dement. 2025 May;21(5):e70228. PubMed.
103. Handen BL, Mapstone M, Hartley S, Andrews H, Christian B, Lee JH, Tudorascu D, Hom C, Ances BM, Zaman S, Krinsky-McHale S, Brickman AM, Rosas HD, Cohen A, Petersen M, O'Bryant S, Harp JP, Schmitt F, Ptomey L, Burns J, Lott IT, Lai F, Silverman W, Laymon C, Head E, Alzheimer's Biomarker Consortium – Down Syndrome (ABC‐DS). The Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS): A 10-year report. Alzheimers Dement. 2025 May;21(5):e70294. PubMed.
104. Videla L, Benejam B, Barroeta I, Fernandez S, Altuna M, Arranz J, Rodríguez-Baz Í, Arriola-Infante JE, Maure-Blesa L, Del Hoyo Soriano L, Illán-Gala I, Estellés T, Sanjuan A, Vaqué-Alcázar L, Aranha MR, Morcillo-Nieto AO, Zsadanyi SE, Franquesa-Mullerat M, Valldeneu S, Sánchez-Saudinós MB, Padilla C, Carreras M, Lorente O, Valle-Tamayo N, Sánchez-Aced É, Dols-Icardo O, Sirisi S, Muñoz L, Torres S, Bounasr El Bennadi SE, Sánchez O, Garzón D, Ribas L, Elbachiri S, Mota C, Tondo M, Camacho V, Giménez S, Delaby C, Belbin O, Iulita MF, Montal V, Pegueroles J, Vilaplana E, Clarimón J, González-Ortiz S, Molina-Porcel L, Aldecoa I, Alcolea D, Bejanin A, Videla S, Blesa R, Lleó A, Carmona-Iragui M, Fortea J. The Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) and its contributions to understanding Alzheimer's disease in Down syndrome: A decade of discovery. Alzheimers Dement. 2025 Jun;21(6):e70259. PubMed.
105. Barroeta I, Videla L, Carmona-Iragui M, Fortea J, Rafii MS. Current advances and unmet needs in Alzheimer's disease trials for individuals with Down syndrome: Navigating new therapeutic frontiers. Alzheimers Dement. 2025 Jun;21(6):e70258. PubMed.
106. Hillerstrom H, Fisher R, Janicki MP, Chicoine B, Christian BT, Esbensen A, Esralew L, Fortea J, Hartley S, Hassenstab J, Keller SM, Krinsky-McHale S, Lai F, Levin J, McCarron M, McDade E, Rebillat AS, Rosas HD, Silverman W, Strydom A, Zaman SH, Zetterberg H. Adapting prescribing criteria for amyloid-targeted antibodies for adults with Down syndrome. Alzheimers Dement. 2024 May;20(5):3649-3656. Epub 2024 Mar 13 PubMed.
107. Geerts H, Bergeler S, Walker M, Rose RH, van der Graaf PH. Quantitative systems pharmacology-based exploration of relevant anti-amyloid therapy challenges in clinical practice. Alzheimers Dement (N Y). 2024;10(2):e12474. Epub 2024 May 21 PubMed.
108. Krasny S, Yan C, Hartley SL, Handen BL, Wisch JK, Boehrwinkle AH, Ances BM, Rafii MS, ABC‐DS consortium. Assessing amyloid PET positivity and cognitive function in Down syndrome to guide clinical trials targeting amyloid. Alzheimers Dement. 2024 Aug;20(8):5570-5577. Epub 2024 Jun 28 PubMed.
109. Liu L, Saba A, Pascual JR, Miller MB, Hennessey EL, Lott IT, Brickman AM, Wilcock DM, Harp JP, Schmitt FA, Selkoe DJ, Chhatwal JP, Head E. Lecanemab and Vascular-Amyloid Deposition in Brains of People With Down Syndrome. JAMA Neurol. 2024 Oct 1;81(10):1066-1072. PubMed.
110. Thirumalai S, Livesey FJ, Patani R, Hung C. APP antisense oligonucleotides are effective in rescuing mitochondrial phenotypes in human iPSC-derived trisomy 21 astrocytes. Alzheimers Dement. 2025 Jan;21(1):e14560. PubMed.
111. Herault Y, Delabar JM, Fisher EM, Tybulewicz VL, Yu E, Brault V. Rodent models in Down syndrome research: impact and future opportunities. Dis Model Mech. 2017 Oct 1;10(10):1165-1186. PubMed.
112. Farrell C, Mumford P, Wiseman FK. Rodent Modeling of Alzheimer's Disease in Down Syndrome: In vivo and ex vivo Approaches. Front Neurosci. 2022;16:909669. Epub 2022 Jun 7 PubMed.
113. Clas GS, Marazita M, Pertierra L, Vazquez S, Isaja L, Rodríguez-Varela S, Mucci S, Helou B, Tapajóz F, Magrath N, Bérgamo Y, Allegri R, Sevlever GE, Scassa ME, Surace EI, Romorini L. Generation of human induced pluripotent stem cell lines from two down syndrome patients, including a down syndrome/Alzheimer's disease case (FLENIi002-A) and a beta-amyloid-resistant case (FLENIi003-A). Stem Cell Res. 2025 May 1;86:103728. Epub 2025 May 1 PubMed.
114. Fertan E, Böken D, Murray A, Danial JS, Lam JY, Wu Y, Goh PA, Alić I, Cheetham MR, Lobanova E, Zhang YP, Nižetić D, Klenerman D. Cerebral organoids with chromosome 21 trisomy secrete Alzheimer's disease-related soluble aggregates detectable by single-molecule-fluorescence and super-resolution microscopy. Mol Psychiatry. 2024 Feb;29(2):369-386. Epub 2023 Dec 15 PubMed.

Other Citations

1. duplications

External Citations

1. NCT06673069

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