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Barthélemy NR, Bateman RJ, Hirtz C, Marin P, Becher F, Sato C, Gabelle A, Lehmann S. Cerebrospinal fluid phospho-tau T217 outperforms T181 as a biomarker for the differential diagnosis of Alzheimer's disease and PET amyloid-positive patient identification. Alzheimers Res Ther. 2020 Mar 17;12(1):26. PubMed.
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Washington University
This study by Janelidze et al. is a timely contribution to the field of tau-related AD diagnostics. This study highlights the value of using newer diagnostic platforms to explore additional phosphorylation sites in the CSF of AD. By assessing the association between phosphorylated tau217 (p-tau217) and aggregated amyloid (amyloid PET) and tau (tau PET) at various stages they were able to demonstrate that, compared to p-tau181 and total tau, p-tau217 was better at discriminating AD from non-AD dementias, demonstrated statistically significantly stronger associations with amyloid and tau PET (albeit, relatively small differences), and was reproducible in different cohorts and with different platforms used to measure it. All in all, this study, along with recently published studies assessing p-tau217 levels in the CNS, indicate that this soluble tau-related biomarker is here to stay. Whether it is truly superior to p-tau181 or complementary is not necessarily clear to me. However, given the recently reported performance of plasma p-tau181 in discriminating AD from non-AD cohorts and identifying the presence of elevated tau PET levels reported by these authors in this same cohort (Janelidze et al., 2020), it is unfortunate that a comparison between the CSF p-tau217 and plasma p-tau181 was not performed in this work.
These results strongly support those from our recently published study from the DIAN cohort as well as a very similar publication this month from an American and French cohort using a quantitative mass spectrometry method in demonstrating both the very strong association of p-tau217 with amyloid pathology and as a specific biomarker for AD-related dementia (Mar 2010 news on Barthelemy et al., 2020; Barthelemy et al., 2020) Moreover, in the current work the authors compared two different ELISA-based methods for measuring p-tau271 and found comparable results. Given that the previous studies measuring p-tau217 employed mass spectrometry and had largely similar conclusions, overall, this suggests that increased level of p-tau217 in the CSF is a robust marker for AD. As the authors suggest, with validation in larger cohorts, p-tau217 may become the gold standard as an AD diagnostic test, particularly if this phosphorylation site can be reliably detected in the blood.
References:
Barthélemy NR, Li Y, Joseph-Mathurin N, Gordon BA, Hassenstab J, Benzinger TL, Buckles V, Fagan AM, Perrin RJ, Goate AM, Morris JC, Karch CM, Xiong C, Allegri R, Mendez PC, Berman SB, Ikeuchi T, Mori H, Shimada H, Shoji M, Suzuki K, Noble J, Farlow M, Chhatwal J, Graff-Radford NR, Salloway S, Schofield PR, Masters CL, Martins RN, O'Connor A, Fox NC, Levin J, Jucker M, Gabelle A, Lehmann S, Sato C, Bateman RJ, McDade E, Dominantly Inherited Alzheimer Network. A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer's disease. Nat Med. 2020 Mar;26(3):398-407. Epub 2020 Mar 11 PubMed.
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