A previously unrecognized large pool of Ap was discovered in freshly drawn
plasma of patients diagnosed with Alzheimer's disease (AD) and non-demented
control subjects. This A beta pool was revealed after acid denaturation an
d chromatographic separation of plasma proteins followed by A beta quantita
tion in the 4.5 kDa fractions by europium immunoassay, The mean values of A
beta 42 in the AD and control individuals amounted to 236 ng/ml and 38 ng/
ml, respectively. These A beta values are on the average far higher than pr
eviously measured. Surprisingly, the circulating A beta 42 is about 16 time
s more abundant than A beta 40 in the AD population, Addition of A beta to
freshly drawn plasma demonstrated the rapid disappearance of A beta epitope
s, as detected by immunochemical techniques, suggesting either proteolytic
degradation or A beta sequestration, Incubation of A beta with purified pla
sma proteins and lipoproteins rapidly decreases detectable levels of free A
beta suggesting epitope masking as the likely mechanism. The free and prot
ein-bound A beta b in the circulation may represent a potential source for
deposition in the cerebrovasculature and brain parenchyma of AD. (C) 1999 A
cademic Press.