Early senile plaques in Alzheimer's disease demonstrated by histochemistry, immunocytochemistry, and electron microscopy.

To clarify early pathologic changes in Alzheimer's disease, the brains from two cases from a single family with this disease were examined. A mother who died at age 75 with severe dementia showed an abundance of typical senile plaques, neurofibrillary tangles, and cerebrovascular amyloidosis. The senile plaque and cerebrovascular amyloid were strongly immunoreactive to anti-beta protein antibody. Her son manifested erratic and bizarre behavior, and was suspected of having committed suicide at age 52. His brain weight and macroscopic observations were normal; however, Bielschowsky's silver impregnation and methenamine silver stains showed numerous argyrophilic plaque-like lesions in the neocortex. They were weakly immunolabeled by anti-beta protein antibody, but lacked any abnormal neurites of Congophilic amyloid deposits. These lesions resembled the "type 3" immunoreactive lesions (previously reported by us in Alzheimer's disease and Down's syndrome) which seem to be an early stage of senile plaque formation. These putative early plaque lesions were also examined by methenamine silver electron microscopy, and were seen to consist of loose aggregations of irregular spindle-shaped structures with a heavy deposition of silver grains, with genuine amyloid fibrils not being apparent. It is believed that the accumulation of beta-protein immunoreactive material without amyloid fibril formation might be an initial step in the development of the senile plaque, and that the son, having extensive cortical involvement with type 3 plaque lesions, demonstrated clinical manifestations of less completely developed Alzheimer's disease.