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May 7, 2014

Gene Variant Protects against Brain Aging

  • A particular gene, called WWC1, is known to have variants associated with human memory performance. While a population of individuals possessing the “good” variant may perform better on memory tests than less fortunate populations, individuals from either group may or may not show differences in age-related declines. That is, variants of the WWC1 gene, which encodes the kidney and brain expressed (KIBRA) protein, may or may not have a role in brain aging.

    To trace the influences of WWC1 variants over time, scientists need more than a snapshot of memory performance. A kind of snapshot might be assembled from measurements provided by individuals who are all approximately the same age. The equivalent of a time-lapse film, however, might be developed if scientists at least examine a population of people who range in age.

    This approach, in fact, was taken by researchers at the Lieber Institute for Brain Development and the National Institute of Mental Health, led by senior author Venkata Mattay, M.D. They recruited 233 healthy volunteers who ranged in age from 18 to 89 years. The volunteers completed a battery of cognitive tests, underwent genotyping, and completed a memory task during a brain imaging scan. The volunteers were, in effect, examined by means of genetic imaging.

    The brain scans, which were taken via functional magnetic imaging (fMRI), were used to assess differences in hippocampal engagement during episodic memory (EM) tests. These differences were correlated with other data, which in addition to subject age included each subject’s particular WWC1 variant. In this study, the variants had three potential forms: CC, TT, or CT.

    The researchers found that individuals who carry the T allele, as either CT or TT, performed better on the memory task and showed more active engagement in the hippocampus, a vital brain region for memory, with increasing age. This finding appeared May 1, in the print edition of Biological Psychiatry, in an article entitled, “WWC1 Genotype Modulates Age-Related Decline in Episodic Memory Function Across the Adult Life Span.”

    “Our results show a dynamic relationship between this gene and increasing age on hippocampal function and episodic memory with the non-T allele group showing a significant decline across the adult life span,” said Dr. Mattay. “A similar relationship was not observed in the T-allele carrying group suggesting that this variant of the gene may confer a protective effect.”

    Dr. Mattay speculated on the significance of these results as follows: “Identifying these genetic factors, while helping us better understand the neurobiology of cognitive aging, will also aid in identifying mechanisms that confer individuals with resilience to withstand the inevitable age-related changes in neural architecture and function.” In addition, John Krystal, M.D., editor of Biological Psychiatry, commented, “The risk mechanisms for age-related memory impairment that we identify today may become the targets for the prevention and treatment of this problem in the future.”


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