Uhlmann RE, Rother C, Rasmussen J, Schelle J, Bergmann C, Ullrich Gavilanes EM, Fritschi SK, Buehler A, Baumann F, Skodras A, Al-Shaana R, Beschorner N, Ye L, Kaeser SA, Obermüller U, Christensen S, Kartberg F, Stavenhagen JB, Rahfeld JU, Cynis H, Qian F, Weinreb PH, Bussiere T, Walker LC, Staufenbiel M, Jucker M. Acute targeting of pre-amyloid seeds in transgenic mice reduces Alzheimer-like pathology later in life. Nat Neurosci. 2020 Dec;23(12):1580-1588. Epub 2020 Nov 16 PubMed.

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Comments

  1. I hope that this experiment can be repeated in a human CD33 transgenic mouse that has been crossed into an Alzheimer's model. There is strong unpublished evidence to suggest that CD33 is involved in the regulation of the phagocytosis or trogocytosis of neurotoxic, minuscule synaptic amyloid seeds within the synaptic space. There are several CD33 antibodies that have had safe profiles in clinical trials that could be tried, such as lintuzumab or gemtuzumab. It is possible that a combination of one of these and aducanumab might be effective at very early stages of the disease.

    View all comments by Eileen Press

  2. Suppressing or slowing the progression of AD is thought to be a pathological condition shown in the reference paper. It has been shown that even if Aβ is deposited, disease onset can be suppressed or delayed by suppressing the spread of tau pathology. This suggests that there is little association between Aβ deposition and AD progression.

    Anti-Aβ antibodies are thought to work effectively against Aβ amyloidosis, reducing Aβ amyloid. Amyloid deposition at synapses will decrease and transmission will improve. It is thought that some improvement in cognitive function can be seen, but it may not be effective in the progression of AD.

    References:

    Arboleda-Velasquez JF, Lopera F, O'Hare M, Delgado-Tirado S, Marino C, Chmielewska N, Saez-Torres KL, Amarnani D, Schultz AP, Sperling RA, Leyton-Cifuentes D, Chen K, Baena A, Aguillon D, Rios-Romenets S, Giraldo M, Guzmán-Vélez E, Norton DJ, Pardilla-Delgado E, Artola A, Sanchez JS, Acosta-Uribe J, Lalli M, Kosik KS, Huentelman MJ, Zetterberg H, Blennow K, Reiman RA, Luo J, Chen Y, Thiyyagura P, Su Y, Jun GR, Naymik M, Gai X, Bootwalla M, Ji J, Shen L, Miller JB, Kim LA, Tariot PN, Johnson KA, Reiman EM, Quiroz YT. Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report. Nat Med. 2019 Nov;25(11):1680-1683. Epub 2019 Nov 4 PubMed.

    View all comments by Fuyuki Kametani

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  1. In Mice, Aducanumab Neutralizes Aβ Seeds