Two new genetic factors, in addition to previously studied genetic variants, may be associated with the development and progression of Alzheimer’s disease, and there may be an association between genetic factors and neuroimaging traits, according to a study completed at Massachusetts General Hospital in Boston and published June 14 in the Archives of Neurology.
“The mechanisms underlying Alzheimer’s disease onset and progression remain largely unexplained…The demonstration that recently discovered genetic risk factors for Alzheimer’s disease also influence these neuroimaging traits would provide important confirmation of a role for these genetic variants and suggest mechanisms through which they might be acting,” wrote lead study authors Alessandro Biffi, MD, and Christopher D. Anderson, MD, along with their colleagues.
APOE, a genetic variant , was the only previously studied genetic factor shown to influence Alzheimer’s disease risk and age at onset. However, new findings from genome-wide association studies have identified three additional loci that also may point to risk of Alzheimer’s disease.
Researchers recruited 168 individuals with probable Alzheimer's disease and 357 with mild cognitive impairment from more than 50 Alzheimer’s Disease Neuroimaging Initiative centers in the U.S. and Canada and compared them to a control group of 215 cognitively normal individuals to observe the associations between genes and neuroimaging results.
The researchers investigated the effect of the previously studied genetic variants, in addition to two new target gene locations— BIN1 and CNTN5—on hippocampal volume, amygdala volume, white matter lesion volume, entorhinal cortex thickness, parahippocampal gyrus thickness and temporal pole cortex thickness in each of the study participants. They determined that the APOE gene had the strongest association with clinical Alzheimer’s disease and was associated with all neuroimaging traits except white matter lesion volume. The other candidate genes showed a significant cumulative effect on the neuroimaging measures analyzed.
In addition, the two new loci, BIN1and CNTN5, showed association with multiple MR imaging characteristics of Alzheimer’s disease.
“Although our results for these loci can only be considered preliminary, they may help prioritize targets for future genetic studies and genome-wide association studies in Alzheimer’s disease, particularly given their association with neuroimaging correlates of Alzheimer’s disease and disease status,” the authors wrote.
“Our results indicate that APOE and other previously validated loci for Alzheimer’s disease affect clinical diagnosis of Alzheimer’s disease and neuroimaging measures associated with disease,” they concluded. “These findings suggest that sequence variants that modulate Alzheimer’s disease risk in recent genome-wide association studies may act through their influence on neuroimaging measures.”