Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Department of Biological Sciences, Markey Center for Structural Biology, Purdue University, West Lafayette, IN, USA.
Nat Struct Mol Biol. 2024 Jun;31(6):903-909. doi: 10.1038/s41594-024-01252-3. Epub 2024 Mar 29.
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 Aβ filaments (types IIIa and IIIb) that differ from those previously reported in sporadic AD and two types of Aβ 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.
患有唐氏综合征（DS）的成年个体可发展为阿尔茨海默病（AD）。AD 在 DS 中的结构与 AD 是否存在差异，关于淀粉样蛋白-β（Aβ）和 tau 丝的结构尚不清楚。在这里，我们报告了来自两个 DS 大脑的 Aβ 和 tau 丝的结构。我们发现了两种 Aβ 丝（IIIa 和 IIIb 型），它们与先前在散发性 AD 中报道的不同，以及两种 Aβ 丝（I 和 II）与散发性和家族性 AD 中发现的相同。tau 丝（双螺旋丝和直丝）与 AD 中的相同，这支持了淀粉样蛋白通过触发 tau 聚集的共同机制的观点。这一知识对于理解 DS 中的 AD 以及评估是否可以将 DS 患者纳入 AD 临床试验非常重要。
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