Study Shows Shared Genetic Risks for Alzheimer’s and Autoimmune Disease Interview with:

Jennifer S. Yokoyama, PhD Assistant Professor, Memory and Aging Center University of California, San Francisco

Dr. Yokoyama

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. What should clinicians and patients take away from your report?

Dr. Yokoyama: Taken together, our study shows that there are shared genetic risk factors for Alzheimer’s disease and autoimmune disease. This suggests that immune processes may directly contribute to Alzheimer’s pathology and disease progression rather than emerge as a byproduct of the disease. This does not mean that people with autoimmune disease will necessarily develop Alzheimer’s disease. Rather, this association suggests that shared biological pathways may underlie both autoimmune disease and Alzheimer’s disease. Gauging an individual’s risk of Alzheimer’s disease is complex, and there are numerous genetic variants, environmental factors, and lifestyle choices that influence an individual’s likelihood of developing Alzheimer’s disease. We think our study offers an important inroad into the Alzheimer’s disease process and points to biological systems that might be amenable to therapeutic intervention. The broader goal of our research is to work toward defining all of the myriad risk factors for Alzheimer’s disease so that one day we can use this information in the clinic. A more comprehensive understanding of the genetic variants that contribute to Alzheimer’s disease will help clinicians to evaluate risk in individuals and to develop effective treatment plans that are tailored to their needs. It may be helpful for clinicians to be aware of potential links between autoimmune disease and cognition because subtle declines in cognitive functioning may be early signs of an underlying neurodegenerative process. What recommendations do you have for future research as a result of this study?

Dr. Yokoyama: More research is required to identify the biological contribution of these genetic variants to Alzheimer’s disease. Future research is also required to test whether any of these pathways may serve as new targets for treating clinical symptoms of Alzheimer’s disease. Is there anything else you would like to add?

Dr. Yokoyama: In addition to establishing a common genetic link between Alzheimer’s and autoimmune diseases, we have also created an analytical framework by which other researchers can test for genetic variants that contribute to other diseases and traits that may share underlying biology.


Yokoyama JS, Wang Y, Schork AJ, et al. Association Between Genetic Traits for Immune-Mediated Diseases and Alzheimer Disease. JAMA Neurol. Published online April 18, 2016. doi:10.1001/jamaneurol.2016.0150.

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Last Updated on April 20, 2016 by Marie Benz MD FAAD