Relative abundance of Alzheimer Aβ amyloid peptide variants in Alzheimer disease and normal aging

The Alzheimer Aβ amyloid peptide (Aβ) is the principal proteinaceous component of amyloid associated with Alzheimer disease (AD). We have determined the relative abundance of Aβ 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 Aβ amyloid was used. The purified, nondigested Aβ was analyzed by N-terminal sequencing and electrospray- ionization mass spectrometry. Three principal Aβ variants were detected- Aβ-(1-40), Aβ-(1-42), and Aβ-(11-42)-in all brains analyzed. The predominant variant in sporadic AD was Aβ-(1-40), whereas the principal Aβ variant in nondemented elderly controls was Aβ-(1-42). The ratio Aβ-(1- 40)/Aβ-(1-42) differed by 10-fold between brains from nondemented controls and those with sporadic AD.