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Analysis finds gene variants associated with Alzheimer's amyloid deposition

NIA-supported researchers combined images of the brains of older people with Alzheimer’s or at risk for the disease with their genetic data to find a previously unknown link between the gene for butyrlcholinesterase (BCHE) and beta-amyloid deposition in the brain. Beta-amyloid is the major constituent of plaques, a hallmark of Alzheimer’s disease. In addition to BCHE, the study showed that apolipoprotein-E (APOE), a known genetic risk factor for Alzheimer’s, was also associated with the level of amyloid found in the brain. These findings offer new insights into Alzheimer’s disease pathways and promising targets for therapies that may delay, prevent, or treat the disease.

Scientists at the Indiana University School of Medicine, Indianapolis, led a national team of researchers conducting the genome-wide association study that studied thousands of genetic variants to test whether any could be associated with plaque deposits. Amyloid plaques are of interest in Alzheimer’s research because they build up in the brains of people with the disorder and may play a role in disease onset and progress.

The researchers imaged the brains of 555 volunteers using positron emission topography (PET) scans with florbetapir, a specialized tracer that binds to amyloid in the brain. When the imaging data were combined with the DNA analysis, the researchers found that volunteers with the BCHE gene had greater amounts of amyloid. Of note, the BCHE gene codes for an enzyme that breaks down acetylcholine, an important neurotransmitter that is known to be lost in the early stages of the disease.

The effect of BCHE was independent of the APOE gene variant. However, volunteers with both gene variants had more amyloid deposition than those with a single suspect gene. The volunteers are part of the NIA-supported Alzheimer’s Disease Neuroimaging Initiative (ADNI), the largest public-private partnership to date in Alzheimer’s research. ADNI’s goal is to find neuroimaging and other biological markers that can detect disease progression and measure the effectiveness of potential therapies.

Reference: Ramanan VK, et al. APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study. Molecular Psychiatry. Published online, Feb. 19, 2013. doi: 10.1038/mp.2013.19.