Heterogeneity of water‐soluble amyloid β‐peptide in Alzheimer's disease and Down's syndrome brains

FEBS Letters

Tabaton, Massimo²  DeBusk, Laura M.¹  Gambetti, Pierluigi¹  Russo, Claudio¹  Teller, Jan K.¹  Saido, Takaomi C.³ 

[1] Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA;Institute of Human Anatomy, University of Genova, 16132 Genova, Italy;Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan

关键词: Amyloid beta-peptide;    Alzheimer's disease;    Down's syndrome;    Pyroglutamate;    Aβ;    amyloid β peptide;    AD;    Alzheimer's disease;    APP;    amyloid precursor protein;    DS;    Down's syndrome;    pE;    pyroglutamate;    sAβ;    water-soluble Aβ;   

DOI  :  10.1016/S0014-5793(97)00564-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Water-soluble amyloid β-peptides (sAβ), ending at residue 42, precede amyloid plaques in Down's syndrome (DS). Here we report that sAβ consists of the full-length Aβ_1–42 and peptides truncated and modified by cyclization of the N-terminal glutamates, Aβ_3(pE)–42 and Aβ_11(pE)–42. The Aβ_3(pE)–42 peptide is the most abundant form of sAβ in Alzheimer's disease (AD) brains. In DS, sAβ_3(pE)–42 concentration increases with age and the peptide becomes a dominant species in the presence of plaques. Both pyroglutamate-modified peptides and the full-length Aβ form a stable aggregate that is water soluble. The findings point to a crucial role of the aggregated and modified sAβ in the plaque formation and pathogenesis of AD.

【 授权许可】

Unknown