An international team of researchers, led by Columbia University Medical Center, Boston University School of Medicine and the University of Toronto, has uncovered a major new gene — SORL1 — implicated in late-onset Alzheimer’s disease. Replicated in four distinct ethnic groups, SORL1 is only the second genetic variant for late-onset Alzheimer’s, the type of Alzheimer’s found in 90 percent of people with this devastating disease. ApoE4, the first, was identified in 1993.
In an article published in the Jan. 14 advance on-line edition of Nature Genetics (February print edition), researchers describe how variants in the SORL1 gene were found to be more common in people with late-onset Alzheimer’s than in healthy people the same age. The authors believe that these genetic variants alter the normal function of SORL1, sending amyloid precursor protein (APP) down a pathway that increases the production of the toxic amyloid beta (A?]) peptides in the brain resulting in Alzheimer’s. When the SORL1 gene works properly, it sends APP along recycling pathways — preventing it from being cut into toxic A?] forms.
People with these genetic variants may not produce normal amounts of SORL1, suggesting that this gene has protective function when working properly. The researchers believe that the reduction of SORL1 in the brain increases the likelihood of developing Alzheimer’s disease.
An important aspect of their findings was that the association between Alzheimer’s disease and SORL1 was replicated in four distinct ethnic groups: Caribbean-Hispanics, North Europeans, African-Americans and Israeli-Arabs. Many previous studies on the genetics of Alzheimer’s used data from mostly white populations of American and European ancestry. In total, the five-year federally- and internationally-funded study involved DNA samples from 6,000 volunteers.
The research team at Columbia University Medical Center was led by Richard Mayeux, M.D., co-director of the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain. The team at the University of Toronto was led by Peter St. George-Hyslop, M.D., director of the Centre for Research in Neurodegenerative Diseases, and the Boston University team by Lindsay Farrer, Ph.D., chief of the Genetics Program. Steven Younkin, M.D., Ph.D., chair of Department of Pharmacology at the Mayo Clinic College of Medicine in Jacksonville, Fla. also provided DNA samples from the Mayo’s respective unique populations for the study.