Alzheimer's Gene Linked to Lower Brain Amyloid


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The U.S. National Institutes of Health (NIH) today announced that researchers investigating a gene known to increase the risk of Alzheimer's have discovered the gene is also associated with lower levels of beta amyloid in healthy older people. This finding throws into question the current hypothesis in Alzheimer's research that holds increasing beta amyloid levels are a large part of the disease. Beta amyloid is a brain protein that is a main component of deposits found in the brains of Alzheimer's patients.

"The prevailing hypothesis has implicated factors increasing beta amyloid in the brain as an integral element of Alzheimer's disease pathology," said Dr. Richard Hodes, National Institute on Aging (NIA) director. " This study indicates the importance of exploring and understanding other distinct mechanisms that may be at work in this disease."

Researchers used brain scans to measure brain amyloid in 57 "cognitively normal" older people from the Baltimore Longitudinal Study of Aging (BLSA) and 22 "cognitively normal" people from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The participants were age 78.5 on average. They found that 17 of the BLSA participants and four of the ADNI participants carried the Alzheimer's risk variant of the complement receptor-1 (CR1) gene.

"We found that brain amyloid burden in the group with the CR1 risk variant was lower than in the group without it," said Dr. Madhav Thambisetty, lead author of the study and chief of the Clinical and Translational Neuroscience Unit in the Laboratory of Behavioral Neuroscience of the NIA's Intramural Research Program. This difference in brain amyloid between the two groups is statistically significant in several brain regions. That suggests to us that the CR1 risk factor gene, if it contributes to Alzheimer’s disease, does it in a way unrelated to increasing amyloid burden.

"The findings suggest that the increased risk of Alzheimer's associated with CR1 is not driven by an increase in amyloid in the brain and that we may also need to consider multiple genetic risk factors in combination. It may be possible that CR1 acts through other mechanisms, distinct from those that increase amyloid deposition in the brain. These may include influencing inflammation in the brain, but further research is needed to identify what these other mechanisms might be."

The study was a joint effort by the NIH and NIA. It was recently published in the journal Biological Psychiatry.