New gene increases Alzheimer’s risk

Replicated in four distinct ethnic groups, SORL1 is only the second gene discovered for late-onset Alzheimer’s. APOE, the first gene, was identified in 1993.

The 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. People with these genetic variants may not produce normal amounts of SORL1, suggesting that this gene has a protective function when working properly. The researchers believe that the reduction of SORL1 in the brain increases the likelihood of developing Alzheimer disease.

An important aspect of their findings was that the association between Alzheimer disease and SORL1 was replicated in four distinct ethnic groups: North American and European Caucasians, African-Americans, Caribbean-Hispanics, and Arabs residing in Israel.

The scientists believe the work illustrates the value of diverse populations and international collaborations for understanding a complex disease such as Alzheimer’s. The discovery of the new gene also suggests new ways in which therapies can be developed.

“Understanding how the forms of the SORL1 gene associated with increase risk alter protein handling will suggest novel pharmacological or lifestyle modifications to slow progression,” noted Robert Friedland, professor in the Department of Neurology at Case School of Medicine.

The researchers also noted that there are likely to be more other important genetic variants that need to be identified before the entire picture is complete

“While we have identified several variants in SORL1 that show the same pattern of association across multiple ethnic groups with very different genetic makeup and lifestyle characteristics, it is unclear whether these variants influence the disease process directly or merely mark the location in the SORL1 gene of the biologically important variants, which have not yet been tested,” said Boston University School of Medicine chief of genetics Linday Farrer.