MedicalResearch.com Interview with: Steve Estus PhD
Dept. of Physiology University of Kentucky
Office: Room 332 Sanders-Brown Building
800 S. Limestone Street
Lexington, KY 40536-0230
MedicalResearch.com: What are the main findings of the study?
Answer: We report evidence for the function of a Alzheimer’s genetic risk factor. This protective allele of the polymorphism decreases the splicing efficiency of exon 2 in CD33, a receptor protein that regulates microglial activation. Loss of exon 2 appears to produce a dormant CD33 protein, resulting in increased microglial phagocytosis activity. Overall, these findings confirm and extend recent papers in Neuron and Nature Neuroscience (discussed further in our report) that described decreased CD33 activity with the protective SNP allele.
MedicalResearch.com: Were any of the findings unexpected?
Answer: When we found that the polymorphism did not have a robust effect on gene expression, we hypothesized that the polymorphism would alter splicing. The robustness of the splicing results from the human brain were unexpected, some of the clearest data that we have seen.
MedicalResearch.com: What should clinicians and patients take away from your report?
The spate of recent genetic polymorphisms associated with Alzheimers disease risk are essentially identifying rate-determining steps in pathways that lead to the disease. Our report along with others show that inhibiting CD33 reduces disease risk. If a polymorphism that inhibits CD33 can reduce disease risk, a drug that acts similarly is likely to also reduce Alzheimer’s risk.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Answer: To elucidate the actions of other polymorphisms that modulate AD risk and to try to translate these actions into drugs that act similarly and hopefully with larger effect.
CD33 Alzheimer’s Risk-Altering Polymorphism, CD33 Expression, and Exon 2 Splicing.
Departments of Physiology, Pathology, and Biostatistics, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky 40536.
J Neurosci. 2013 Aug 14;33(33):13320-5. doi: 10.1523/JNEUROSCI.1224-13.2013.