A variant gene involved in Alzheimer's disease has been detected through study of Dominican families living in Manhattan

Nicholas Wade:

The families have about three times the usual incidence of Alzheimer's, a finding that led Dr. Richard Mayeux of Columbia University in 1994 to start looking for anything in their environment that could be touching off the disease.

Finding nothing, Dr. Mayeux decided to search for a genetic cause, a task that seemed worth trying because the Dominican Republic, where the families came from, is a single, long-isolated population in which variant genes are easier to detect.

He enlisted three colleagues who were studying Alzheimer's in other populations, in a strategy of looking for mutations in a set of seven genes. The genes are known to be involved in directing the traffic of proteins inside cells, and are plausible candidates for contributing to Alzheimer's because the disease seems to result from an abnormal buildup of protein inside the nerve cell.

Having genetically screened some 6,000 people, the researchers found that in four of their populations people with Alzheimer's had distinguishing genetic markers in just one of the seven genes, known as SORL1. Patients with the variant forms of the gene produce less of that gene's protein than usual, leading to a different traffic pattern and allowing a particular protein in nerve cells, known as the amyloid precursor protein, to be converted into toxic form.

Columbia researchers identify another Alzheimer's gene

SORL1 Genetic Risks For Alzheimer's Disease