The characteristic microscopic findings of Alzheimer disease include neuritic plaques ("senile plaques") which are extracellular deposits of the amyloid beta-protein (Aß). In the more numerous, smaller diffuse plaques this Aß alone is present as filamentous masses. However, the diagnostic neuritic plaques also have dystrophic dilated and tortuous neurites, microglia, and surrounding reactive astrocytes. These plaques are best seen with a silver stain, as seen here in a case with many plaques of varying size.
The amyloid beta-protein (Aß) is derived by cleavage of the larger amyloid precursor protein (APP). APP is expressed in all mammals. In humans, the APP gene is on chromosome 21. Mutations in the APP gene have been found in familial cases of AD. Mutations in APP increase production of Aß. There are additional genetic mutations that play a role in development of AD. The E4 allele of apolipoprotein E is a major risk for AD of late onset, particularly if both alleles are E4. The gene is located on chromosome 19. Over half of AD patients have the E4 allele. Apo E4 increases levels of Aß in the brain. Mutations in the presenilin 1 gene on chromosome 14 and the presenilin 2 gene on chromosome 1 have been associated with early onset AD. These mutations increase Aß production.