Text Size Normal Text Sizing Button Medium Text Sizing Button Large Text Sizing Button Text Contrast Normal Contrast Button Reverse Contrast ButtonSwitch to Spanish Language Press Room Contact Us Sitemap Sign In Register
Link to Homepage About BrightFocus
BrightFocus
Donate Now Get Involved  
Alzheimer's Disease Research Macular Degeneration Research National Glaucoma Research


Stay Informed: Medical and Research Updates
Connect With Us!
 

 

Risk Gene for Alzheimer's Disease Associated with Lower Brain Amyloid

NIH study reveals multiple mechanisms may play role in complex disorder

October 1, 2012

Source: Biological Psychiatry

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 September 27, 2012 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, M.D. "This study indicates the importance of exploring and understanding other distinct mechanisms that may be at work in this disease."

Using a brain scan called Pittsburgh Compound B positron emission tomography (PiB PET), the researchers measured brain amyloid in 57 cognitively normal older people with an average age of 78.5 in the Baltimore Longitudinal Study of Aging (BLSA). The researchers also looked at PiB PET data from 22 cognitively normal people about the same average age in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Of the 57 BLSA participants, 17 carried the Alzheimer's risk variant of the CR1 gene, while four of the 22 ADNI participants carried the variant.

"We found that brain amyloid burden in the group with the CR1 risk variant was lower than in the group without it. This difference in brain amyloid between the two groups is statistically significant in several brain regions," said lead author Madhav Thambisetty, M.D., Ph.D., chief of the Clinical and Translational Neuroscience Unit in the Laboratory of Behavioral Neuroscience of the NIA's Intramural Research Program. "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," Thambisetty continued. "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."

Adapted from the National Institute on Aging

View all news updates for Alzheimer's disease


Disclaimer: The information provided in this section is a public service of the BrightFocus Foundation, and should not in any way substitute for the advice of a qualified healthcare professional, and is not intended to constitute medical advice. Although we take efforts to keep the medical information on our website updated, we cannot guarantee that the information on our website reflects the most up-to-date research. Please consult your physician for personalized medical advice; all medications and supplements should only be taken under medical supervision. BrightFocus Foundation does not endorse any medical product or therapy.

Some of the content in this section is adapted from other sources, which are clearly identified within each individual item of information.

Shop for a Cause YouTube Twitter Connect With Us Pinterest Google+