A discovery about the brain protein KIBRA, commonly found in the kidneys and brain, could lead to future treatments for Alzheimer disease (AD). Investigators at the Translational Genomics Research Institute (TGen), lead by Corneveaux and Liang, in Phoenix found that the risk for AD is 25% lower in persons who carry the memory-enhancing KIBRA gene.1 This fi nding indicates that there might be a link between KIBRA and some of the proteins with which it interacts.
This group conducted 3 studies and found that AD is less likely to develop in persons who carry the KIBRA T-allele than in those who carry the C-allele.
• Researchers compared genotype samples from more than 1700 living and deceased persons with and without AD and found that noncarriers of the T-allele were more likely to have late-onset AD.
• Investigators also conducted a gene expression study that examined tissues from 6 regions of the brain of 47 deceased persons. They discovered that KIBRA, and a subset of other molecules that directly interacted with it, were signifi cantly altered in regions of the brain involved in AD. Of note, these molecules were not altered in the primary visual cortex, which is typically unaffected by the disease.
• The team obtained PET scans of 69 carriers and 67 noncarriers of the KIBRA T-allele of persons who had close relatives with AD. The scans showed that noncarriers exhibited similar alterations in the metabolic activity of areas of the brain that are altered in the earliest stages of the disease.
The TGen investigators believe that this “variation causes a potential lifelong difference in the total levels of KIBRA in the brain, and that this may infl uence one’s risk for [AD].”