Alzheimer's - Dementia, Author Interviews, JAMA, UCSF / 20.04.2016 Interview with: Jennifer S. Yokoyama, PhD Assistant Professor, Memory and Aging Center University of California, San Francisco What is the background for this study? Dr. Yokoyama: Alzheimer’s disease is a common neurodegenerative disease that occurs in older adults. Clinically, Alzheimer’s disease is primarily associated with changes in cognition (e.g., declines in memory, language and visuospatial functioning). Pathologically, Alzheimer’s disease is associated with misfolded amyloid beta and tau proteins and can only be definitively diagnosed at autopsy. It has long been appreciated that there is a link between the immune system and Alzheimer’s disease, and there are multiple sources of evidence that suggest that immune activity may be increased in patients with Alzheimer’s. Although there is strong evidence for an association between immune activity and Alzheimer’s disease there has always been a chicken-egg problem because we don’t know whether the Alzheimer’s disease process triggers the immune response or whether altered immune function promotes the Alzheimer’s disease process. Genetic information can offer important clues about the role of the immune system in Alzheimer’s disease. Each person has a unique genetic fingerprint, and different combinations of gene changes (“variants”) put individuals at higher or lower risk for different diseases. Genetic data enables us to test whether having a certain genetic variant puts people at greater risk for both Alzheimer’s disease and autoimmune diseases, immune system diseases in which the immune system is overactive (e.g., Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, Celiac's disease, and psoriasis). Rather than only responding to foreign objects such as bacteria and viruses, in autoimmune diseases the immune system also responds to the body’s own material, which do not ordinarily create an immune response, thereby leading to symptoms associated with higher levels of inflammation and other long-term problems. A variant that increases risk for both Alzheimer’s disease and autoimmune diseases would suggest a common biological pathway. What are the main findings? Dr. Yokoyama: In our study we tested whether there are genetic variants that put people at increased risk for both Alzheimer's disease and autoimmune diseases. We found eight genetic variants that influence people’s risk for both Alzheimer's disease and autoimmune disease. Some of these variants were associated with lower risk of autoimmune disease and Alzheimer’s disease, but two variants were associated with greater risk for both.   (more…)