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Heterogeneity of water‐soluble amyloid β‐peptide in Alzheimer's disease and Down's syndrome brains
Author(s) -
Russo Claudio,
Saido Takaomi C.,
DeBusk Laura M.,
Tabaton Massimo,
Gambetti Pierluigi,
Teller Jan K.
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00564-4
Subject(s) - peptide , amyloid beta , beta (programming language) , pathogenesis , p3 peptide , chemistry , amyloid (mycology) , alzheimer's disease , amyloid precursor protein , biochemistry , peptide sequence , bace1 as , disease , medicine , pathology , gene , computer science , programming language
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.