Researchers investigating a known gene risk factor for Alzheimer’s disease discovered it is associated with lower levels of beta amyloid — a brain protein involved in Alzheimer’s — in cognitively healthy older people. The findings suggest that a mechanism other than one related to beta amyloid accumulation may influence disease risk associated with the gene. The study, by researchers at the National Institute on Aging (NIA) at the National Institutes of Health, was published online Sept. 27 in the journal “Biological Psychiatry.”

The scientists studied a variation in the complement receptor-1 (CR1) gene, a newly identified gene associated with risk for late-onset Alzheimer’s disease, in cognitively normal older volunteers. Participants with this gene variant were found to have less brain amyloid than those without the risk variant. In addition, the CR1 gene variant was found to interact with APOE, the most robust genetic risk factor for Alzheimer’s disease, to influence the amount of brain amyloid.

“The prevailing hypothesis has implicated factors increasing beta amyloid in the brain as an integral element of Alzheimer’s disease pathology,” said NIA Director Richard J. Hodes, MD. “This study indicates the importance of exploring and understanding other distinct mechanisms that may be at work in this disease.”