As principal investigator of the MIRAGE Project, a multicenter study of Alzheimer's disease funded by the National Institute on Aging, he oversees a project that examines some 2,000 families with at least one member with Alzheimer's. Farrer and his team collaborated on the discovery of two defective genes-mapping presenilin-1 and -2-that may be responsible for up to 70 percent of early onset of classically inherited Alzheimer's. They have recently localized another gene, implicated in late-onset Alzheimer's, to chromosome 12, and are investigating the presence of the E4 variant of the apolipoprotein E (APOE) gene in an effort to understand the vast majority of cases of Alzheimer's, which are not classically inherited.

A supplemental grant to MIRAGE has afforded Farrer's team the opportunity to study Alzheimer's among the African-American population, which does not show a strong correlation between APOE and the disease. They are also searching for genes connected to Alzheimer's in several genetically isolated communities, including a group in India with the world's lowest known incidence of the disease and an Arab group in Israel in which 20 percent of the population over sixty is afflicted.

With support from the National Alzheimer's Association Farrer is now undertaking a groundbreaking analysis of data from the largest familial kindred in the world, located in Columbia, South America. This extended family group, with nearly 2,000 living members, contains sixty to seventy living people with Alzheimer's - all of whom became ill between their late twenties and late fifties. All have the identical defect in the presenilin genes, as do another 300 or more members of the cohort who have not yet developed the disease. Farrer hypothesizes that the thirty year variation in the age of onset is also genetically determined. He suspects the presence of a genetic "switch" that activates the faulty gene, producing the disease. If he and his team can identify this switch, they may be able to shed light on why Alzheimer's - and perhaps other genetically linked diseases - develops at a certain point in a person's life, and, perhaps, devise methods to delay onset.

Farrer is also engaged in a newly funded NIH project that uses the APOE gene/Alzheimer's disease connection as a model for other diseases - like diabetes or certain forms of breast cancer - in which a faulty gene is implicated in making an individual susceptible to developing a given disease. The study is examining the impact of communicating this information to members of the susceptible population, and is developing best practices for structuring genetic testing and education for these individuals and their families.

In recent epidemiological studies Farrer and his colleagues identified head injury as an independent risk factor for Alzheimer's, and determined that people who regularly consume moderate amounts of alcoholic beverages had approximately one-half the risk of developing Alzheimer's as did non-drinkers. Further information about Professor Farrer and his work is available here.