Heterogeneity of water‐soluble amyloid β‐peptide in Alzheimer's disease and Down's syndrome brains
- 16 June 1997
- journal article
- Published by Wiley in FEBS Letters
- Vol. 409 (3) , 411-416
- https://doi.org/10.1016/s0014-5793(97)00564-4
Abstract
Water-soluble amyloid beta-peptides (sA beta), ending at residue 42, precede amyloid plaques in Down's syndrome (DS). Here we report that sA beta consists of the full-length A beta(1-42) and peptides truncated and modified by cyclization of the N-terminal glutamates, A beta[3(pE)-42] and A beta[11(pE)-42]. The A beta[3(pE)-42] peptide is the most abundant form of sA beta in Alzheimer's disease (AD) brains. In DS, sA beta[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 A beta form a stable aggregate that is water soluble. The findings point to a crucial role of the aggregated and modified sA beta in the plaque formation and pathogenesis of AD.Keywords
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