Immunohistological study of senile brains by using a monoclonal antibody recognizing ? amyloid precursor protein: significance of granular deposits in relation with senile plaques

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Abstract
Immunochemical analyses revealed that a monclonal antibody Am-3 recognized β amyloid precursor protein (βAPP) in senile plaques extracted from Alzheimer's brain, but did not recognize β amyloid protein. Immunohistochemically, however, the staining pattern of Am-3 in frozen section of Alzheimer's brain was almost the same with that of rabbit polyclonal antibody to β amyloid peptide which could recognize both β amyloid protein and βAPP. In other words, βAPP was present in senile plaques of various types, cerebrovascular amyloid and granular deposits. The granular deposits were 5–10 μm in size and laminarily distributed in the 1st, 3rd and 4th layers of cerebral cortex. They were especially abundant in 1st and 4th layers where senile plaques were usually fewer in number. Although the distribution in the cerebral cortex was different between the senile plaques and the granular deposits, the number of the granular deposits was well correlated with that of senile plaques. The granular deposits were negative in Congo-red birefringence, but contained β amyloid protein as well as βAPP fragment judging from positive staining by both Am-3 and polyclonal antibody to synthetic β amyloid peptide. Thus, they could be regarded as “pre-amyloid”.