Alzheimer's disease is a neurodegenerative disorder characterized by the massive and invariant accumulation of amyloid plaques in the brains of affected patients. In many cases Alzheimer's disease occurs in the absence of a prior history of the disease in other family members and is designated as sporadic, whereas in approximately 10% of patients, dominantly transmitted mutations within one of three genes are found. A few mutations have been identified within the gene encoding the β-amyloid precursor protein; however, these mutations account for only about 1–3% of cases with familial Alzheimer's disease. In the majority of autosomal dominant cases (40–50%), mutations have been found in a gene localized to chromosome 14. The responsible gene, now called presenilin-1, has recently been identified and shown to encode a putative seven transmembrane domain protein. Surprisingly, a second highly homologous gene (named presenilin-2) was cloned shortly thereafter. It is localized on human chromosome 1 and is also involved in a small number of cases with familial Alzheimer's disease. Early data suggest that mutations found within the two genes cause early onset Alzheimer's disease by influencing the proteolytic processing of amyloid β-peptide in a pathological manner.