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

A previously unrecognized large pool of Aβ was discovered in freshly drawn plasma of patients diagnosed with Alzheimer's disease (AD) and non-demented control subjects. This Aβ pool was revealed after acid denaturation and chromatographic separation of plasma proteins followed by Aβ quantitation in the 4.5 kDa fractions by europium immunoassay. The mean values of Aβ42 in the AD and control individuals amounted to 236 ng/ml and 38 ng/ml, respectively. These Aβ values are on the average far higher than previously measured. Surprisingly, the circulating Aβ42 is about 16 times more abundant than Aβ40 in the AD population. Addition of Aβ to freshly drawn plasma demonstrated the rapid disappearance of Aβ epitopes, as detected by immunochemical techniques, suggesting either proteolytic degradation or Aβ sequestration. Incubation of Aβ with purified plasma proteins and lipoproteins rapidly decreases detectable levels of free Aβ suggesting epitope masking as the likely mechanism. The free and protein-bound Aβb in the circulation may represent a potential source for deposition in the cerebrovasculature and brain parenchyma of AD.