Relative abundance of Alzheimer A beta amyloid peptide variants in Alzheimer disease and normal aging.
The Alzheimer A beta amyloid peptide (A beta) is the principal proteinaceous component of amyloid associated with Alzheimer disease (AD). We have determined the relative abundance of A beta structural variants present in amyloid from brains of 10 individuals with sporadic AD, 2 individuals with familial AD carrying specific mutations in the Alzheimer amyloid precursor protein gene, and 5 nondemented elderly controls. A procedure of isolation based on the extreme insolubility of A beta amyloid was used. The purified, nondigested A beta was analyzed by N-terminal sequencing and electrospray-ionization mass spectrometry. Three principal A beta variants were detected--A beta-(1-40), A beta-(1-42), and A beta-(11-42)--in all brains analyzed. The predominant variant in sporadic AD was A beta-(1-40), whereas the principal A beta variant in nondemented elderly controls was A beta-(1-42). The ratio A beta-(1-40)/A beta-(1-42) differed by 10-fold between brains from nondemented controls and those with sporadic AD.
Näslund
J
J
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Schierhorn
A
A
Hellman
U
U
Lannfelt
L
L
Roses
A D
AD
Tjernberg
L O
LO
Silberring
J
J
Gandy
S E
SE
Winblad
B
B
Greengard
P
P
D000368:Aged; D000375:Aging; D000544:Alzheimer Disease / Q000235:genetics*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D002540:Cerebral Cortex / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009154:Mutation
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor