Association of autoimmune diseases with Alzheimer?s disease: A mendelian randomization study

Background: Alzheimer's disease may have an autoimmune component, but the association is unclear. Objective: The objective of this Mendelian randomization (MR) study was to evaluate the association of liability to autoimmune diseases with Alzheimer's disease Methods: A systematic search was done using PubMed to identify autoimmune diseases that have been suggested as associated with Alzheimer's disease. Genetic predictors of these autoimmune diseases were obtained from the largest and most recent genome-wide association studies (GWAS). Genetic associations with clinically-diagnosed Alzheimer's disease were obtained from the International Genomics of Alzheimer's Project GWAS (21982 cases; 41944 controls); and with parental and sibling history of Alzheimer's disease from the UK Biobank GWAS (27696 maternal, 14338 paternal and 2171 sibling cases). MR estimates were obtained using inverse variance weighting, MR-Egger and weighted median. To address possible selection bias due to inevitably recruiting only survivors, the analysis was repeated in younger people, i.e., UK Biobank siblings and adjusting for competing risk of Alzheimer's disease.Results: Of the 7 autoimmune diseases considered, liability to psoriasis and sarcoidosis were not associated with Alzheimer's disease. Some evidence was found for liability to multiple sclerosis being associated with higher risk and liability to Sjogren's syndrome with lower risk of Alzheimer's disease. Associations found for liability to giant cell arteritis, type 1 diabetes and rheumatoid arthritis were inconsistent in sensitivity analyses.Conclusion: Liability to multiple sclerosis and Sjogren's syndrome could be associated with Alzheimer's disease. The underlying mechanisms, such as the role of myelin and neuroinflammation, should be further investigated.