The discovery of nonbeta-amyloid (Abeta), plaque-like deposits composed of a 100-kd protein (AMY) in sporadic AD (SAD) brains prompted us to determine whether these plaques (AMY plaques) also occur in AD due to mutations of the presenilin-1 (PS-1), presenilin-2 (PS-2), or the amyloid precursor protein (APP) genes.
Screening of familial cases has so far linked four genes to Alzheimer's disease: amyloid precursor protein, presenilin 1, presenilin 2 and apolipoprotein E. Mutations in the amyloid precursor protein, presenilin 1 and presenilin 2 genes cause the enhanced production of b amyloid that is found in neuritic plaques.
In rare patients with autosomal dominant, early-onset Alzheimer's disease (AD), pathogenic mutations in the genes encoding β-amyloid precursor protein, and the γ-secretase-complex components presenilin-1 and presenilin-2 appear to result in β-amyloid (Aβ) overproduction.
Mutations in the human genes PRESENILIN1 (PSEN1), PRESENILIN2 (PSEN2) and AMYLOID BETA A4 PRECURSOR PROTEIN (APP) have been identified in familial Alzheimer's disease (AD).