Gene identification in Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is the most common cause of dementia in the elderly population. Three genes have been identified that cause the less common early-onset, familial cases of the disease: the amyloid precursor (APP) protein gene on chromosome 21, the presenilin 1 (PSEN1) gene on chromosome 14 and the presenilin 2 (PSEN2) gene on chromosome 1. Mutations in these genes account for << 2% of the total number of AD cases. More than 50% of the cases are late-onset and related to the apolipoprotein E (APOE) gene on chromosome 19. The apolipoprotein E locus is a susceptibility gene, with polymorphisms affecting both risk and age-of-onset of the disease. Intense efforts are underway to identify additional susceptibility genes and promising regions on chromosomes 6, 9, 10 and 12 have been identified through whole genome scans. In addition, the genetic basis of several other non-AD inherited dementias has been unravelled. Discovery of the genetically relevant genes will aid in the elucidation of the pathogenesis of AD. The high-throughput tools of pharmacogenomics for gene-to-function-to-target studies can provide a quicker means of monitoring how mutations and polymorphisms affect model systems’ adaptations to the altered genes, possibly identifying signal transduction or biochemical pathways. This relevant information can then be used for drug target selection and pharmacogenetics.