HETEROGENEITY OF WATER-SOLUBLE AMYLOID BETA-PEPTIDE IN ALZHEIMERS-DISEASE AND DOWNS-SYNDROME BRAINS

Water-soluble amyloid beta-peptides (sA beta), ending at residue 42, p recede 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 a bundant form of sA beta in Alzheimer's disease (AD) brains, In DS, sA beta(3(pE)-42) concentration increases with age and the peptide become s a dominant species in the presence of plaques, Both pyroglutamate-mo dified peptides and the full-length A beta form a stable aggregate tha t is water soluble, The findings point to a crucial role of the aggreg ated and modified sA beta in the plaque formation and pathogenesis of AD. (C) 1997 Federation of European Biochemical Societies.