The role of presenilin in the genetics of Alzheimer's disease

Approximately 75% of AD patients have an onset of the disease after the age of 60 years, and 60% of AD patients have no family history of the disease. Some cases of EOAD are clearly inherited in an autosomal-dominant manner. The beta APP gene on chromosome 21, the PS-1 gene on chromosome 14, and the PS-2 gene on chromosome 1 have all been characterized as genes in which mutations lead to familial EOAD. For LOAD, the work on ApoE indicates that the epsilon 4 allele is a risk factor for developing AD. However, 35-50% of all AD patients do not have an epsilon 4 allele. Other loci contributing to LOAD remain to be mapped and characterized. As in other complex disorders, these additional loci may involve genetic interactions with the known AD loci. Identification of all susceptibility loci for AD is a major goal in resolving the pathogenesis of AD.

Clark, R., Hutton, M., Talbot, C., Wragg, M., Lendon, C., Busfield, F., ... Goate, A. (1996). The role of presenilin in the genetics of Alzheimer's disease. Cold Spring Harbor Symposia on Quantitative Biology, 61(1), 551 - 558.