Soluble β‐amyloid concentration corresponds to Alzheimer's disease progression

In Alzheimer's disease (AD) insoluble amyloid plaques have shown weak correlation with clinical measures, but total soluble β‐amyloid (Aβ) has been suggested by the literature as a better marker. Human brain samples were analyzed for soluble Aβ content. Seven subjects with clear pathology were classified according to diagnosis of AD, Braak stages, and presence of Lewy Bodies. Diagnosis and AD staging employed cognitive measures. Autopsy brain samples were homogenized and centrifuged at 100,000 x G for 60 minutes. Total soluble Aβ was determined by sandwich ELISA and normalized to total protein concentration. Size fractionation of soluble Aβ from AD brain cortex revealed multiple high molecular weight species depending on the extraction conditions. Multiple populations of weakly associated soluble Aβ oligomers may be present in AD brain. In comparison of brain regions from control‐early‐late stage AD, areas associated with memory and recall had elevated amounts of soluble Aβ only in early AD. Soluble Aβ levels were elevated first in the prefrontal cortex and finally in the motor cortex. Observations in this limited patient sample suggest a correlation between soluble Aβ levels and when functional deficits in that area begin, while insoluble Aβ levels reportedly rise. Decrease of soluble Aβ could indicate partitioning into insoluble forms. Further study involving a larger patient sample and characterization of the soluble species may help define disease progression and provide insight into etiology. Brain samples supplied by the Sanders‐Brown Brain Bank. Research supported by the Chandler School of Medicine and Center on Aging.