beta-Amyloid protein is higher in Alzheimer's disease brains: description of a quantitative biochemical assay

Deposition of beta-amyloid protein (A beta) in senile plaques and in the walls of cerebral vessels is a pathologic hallmark of Alzheimer's disease (AD). The current diagnostic criteria for AD requires the presence of neurofibrillary tangles and a minimum number of senile plaques in cortex. Senile plaques are readily visualized by silver staining or immunocytochemistry using antibodies raised to A beta. Available histochemical and immunocytochemical methods are sensitive but the results may occasionally be variable and sampling from many brain regions is difficult and impractical. This study describes a simple biochemical method for quantifying the A beta load in unfixed brain homogenates. The immunoassay recognizes all forms of A beta deposits (neuritic and diffuse plaques, and cerebrovascular amyloid) and has a sensitivity and specificity comparable to immunocytochemistry. In direct comparisons, results from the dot blot method correspond well with both Western blot analysis of partially purified A beta and plaque counting by immunocytochemistry. In a retrospective series of 39 postmortem AD and control cases, the amount of A beta in brain by dot blot immunoreactivity effectively separated the two groups. Therefore, this method provides a rapid, sensitive, and accurate quantitation of A beta in postmortem brain tissue and represents an alternative approach for studying A beta deposition in aging and AD.