Cryo-EM structures of amyloid-β and tau filaments in Down syndrome

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2024年3月29日

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Anllely Fernandez,
Md Rejaul Hoq,
Grace I. Hallinan,
Daoyi Li,
Sakshibeedu R. Bharath,
Frank S. Vago,
Xiaoqi Zhang,
Kadir A. Ozcan,
Kathy L. Newell,
Holly J. Garringer,
Wen Jiang,
Bernardino Ghetti,
Ruben Vidal

摘要

Adult individuals with Down syndrome (DS) develop Alzheimer disease (AD). Whether there is a difference between AD in DS and AD regarding the structure of amyloid-β (Aβ) and tau filaments is unknown. Here we report the structure of Aβ and tau filaments from two DS brains. We found two Aβ₄₀ filaments (types IIIa and IIIb) that differ from those previously reported in sporadic AD and two types of Aβ₄₂ filaments (I and II) identical to those found in sporadic and familial AD. Tau filaments (paired helical filaments and straight filaments) were identical to those in AD, supporting the notion of a common mechanism through which amyloids trigger aggregation of tau. This knowledge is important for understanding AD in DS and assessing whether adults with DS could be included in AD clinical trials.