Heterogeneity of water-soluble amyloid beta-peptide in Alzheimer's disease and Down's syndrome brains.
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.
Russo
C
C
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Saido
T C
TC
DeBusk
L M
LM
Tabaton
M
M
Gambetti
P
P
Teller
J K
JK
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002540:Cerebral Cortex / Q000737:chemistry*; D002850:Chromatography, Gel; D004314:Down Syndrome / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D006801:Humans; D007120:Immunochemistry; D011761:Pyrrolidonecarboxylic Acid; D012995:Solubility; D014867:Water
D016229:Amyloid beta-Peptides; D014867:Water; D011761:Pyrrolidonecarboxylic Acid