The aqueous phase of Alzheimer's disease brain contains assemblies built from ∼4 and ∼7 kDa Aβ species

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• 作者：Jessica M. Mc Donald^a ; ¹ ; Tiernan T. O'Malley^a ; ^b ; ¹ ; Wen Liu^a ; Alexandra J. Mably^a ; Gunnar Brinkmalm^c ; Erik Portelius^c ; William M. Wittbold III^d ; Matthew P. Frosch^e ; Dominic M. Walsh^a ; ^{dwalsh3@partners.org" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Alzheimer's disease ; Amyloid β-protein ; Oligomers ; SDS-Stable dimer
• 刊名：Alzheimer's & Dementia
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：11
• 期：11
• 页码：1286-1305
• 全文大小：3468 K

文摘

Much knowledge about amyloid β (Aβ) aggregation and toxicity has been acquired using synthetic peptides and mouse models, whereas less is known about soluble Aβ in human brain.

Methods

We analyzed aqueous extracts from multiple AD brains using an array of techniques.

Results

Brains can contain at least four different Aβ assembly forms including: (i) monomers, (ii) a ∼7kDa Aβ species, and larger species (iii) from ∼30-150 kDa, and (iv) >160 kDa. High molecular weight species are by far the most prevalent and appear to be built from ∼7 kDa Aβ species. The ∼7 kDa Aβ species resist denaturation by chaotropic agents and have a higher Aβ42/Aβ40 ratio than monomers, and are unreactive with antibodies to Asp1 of Ab or APP residues N-terminal of Asp1.

Discussion

Further analysis of brain-derived ∼7 kDa Aβ species, the mechanism by which they assemble and the structures they form should reveal therapeutic and diagnostic opportunities.