High levels of circulating Aβ42 are sequestered by plasma proteins in Alzheimer's disease

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 and chromatographic separation of plasma proteins followed by A beta quantitation 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 previously measured. Surprisingly, the circulating A beta 42 is about 16 times 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 epitopes, as detected by immunochemical techniques, suggesting either proteolytic degradation or A beta sequestration, Incubation of A beta with purified plasma proteins and lipoproteins rapidly decreases detectable levels of free A beta suggesting epitope masking as the likely mechanism. The free and protein-bound A beta b in the circulation may represent a potential source for deposition in the cerebrovasculature and brain parenchyma of AD. (C) 1999 Academic Press.