Genetic Liability to Autoimmune Diseases May Affect Alzheimer Disease Risk

Multiple sclerosis and Sjogren syndrome show more associations with Alzheimer disease compared with other autoimmune diseases.

Genetic liability to multiple sclerosis (MS) and Sjogren syndrome may be related to the risk of developing Alzheimer disease (AD), according to a Mendelian randomization (MR) study published in the Journal of Psychiatric Research.

There are currently no effective treatments or preventative measures available for AD, in part because its cause remains unclear. One of the hypotheses is that immune function plays a role in the development of AD. For the study, researchers sought to evaluate whether other autoimmune diseases may be involved with AD risk.

Researchers from The University of Hong Kong searched publication databases for genome-wide association studies (GWAS) of autoimmune diseases. A total of 7 diseases had sufficient GWAS data available. Single nucleotide polymorphisms (SNPs) that strongly and independently predicted giant cell arteritis, MS, psoriasis, rheumatoid arthritis (RA), sarcoidosis, Sjogren syndrome, and type 1 diabetes (T1D) were evaluated using an MR approach for their relationship with AD risk.

None of the candidate SNPs (psoriasis: n=30; RA: n=11; MS: n=9; T1D: n=9; sarcoidosis: n=4; Sjogren syndrome: n=2; and giant cell arteritis: n=1) were in the apolipoprotein E (APOE) gene or directly associated with AD.

Investigation of potential common CNS pathways, such as myelin damage and neuroinflammation, may shed light on the aetiology of Alzheimer’s diseases in the context of autoimmunity.

In the univariate analysis, significant associations were observed between genetic liability to autoimmune diseases and risk for AD as follows:

  • RA and parental AD (odds ratio [OR], 0.94; 95% CI, 0.89-1.00; P =.05),
  • MS and clinical AD (OR, 1.04; 95% CI, 1.00-1.08; P =.049),
  • Sjogren syndrome and maternal AD (OR, 0.93; 95% CI, 0.86-0.99; P =.03),
  • Sjogren syndrome and sibling AD (OR, 0.87; 95% CI, 0.76-0.98; P =.02),
  • Giant cell arteritis and parental AD (OR, 0.85; 95% CI, 0.79-0.90; P <.001),
  • Giant cell arteritis and paternal AD (OR, 0.81; 95% CI, 0.72-0.90; P <.001),
  • Giant cell arteritis and maternal AD (OR, 0.87; 95% CI, 0.80-0.94; P <.001), and
  • Giant cell arteritis and clinical AD (OR, 0.87; 95% CI, 0.81-0.94; P <.001).

No evidence supported the relationship between sarcoidosis (all P ≥.15), psoriasis (all P ≥.15), or T1D (all P ≥.6) and AD risk in the univariate analysis.

In the multivariate analysis, positive associations between genetic liability for MS with clinical AD (odds ratio [OR], 1.04; 95% CI, 1.01-1.07; P =.02) and maternal AD (OR, 1.04; 95% CI, 1.01-1.08; P =.01) were observed. Also, a negative relationship between T1D and clinical AD was observed (OR, 0.94; 95% CI, 0.89-0.99; P =.02).

No evidence supported the relationship between genetic liability to psoriasis (all P ≥.08), RA (all P ≥.22), or sarcoidosis (all P ≥.22) with AD risk in the multivariate analysis.

In the sensitivity analysis, MS remained associated with AD after removing SNPs associated with selective survival (n=1). No other sensitivity analyses could be performed due to the small number of potentially significant SNPs.

This study was limited by the low number of potentially relevant SNPs observed for some of the autoimmune diseases.

“Our results, together with evidence from previous studies suggested Alzheimer’s disease may share causes with multiple sclerosis and Sjogren’s syndrome,” the researchers stated.

They concluded that “Investigation of potential common CNS [central nervous system] pathways, such as myelin damage and neuroinflammation, may shed light on the aetiology of Alzheimer’s diseases in the context of autoimmunity.”


Yeung CHC, Yeung SLA, Schooling CM. Association of autoimmune diseases with Alzheimer’s disease: A mendelian randomization study. J Psychiatr Res. 2022;155:550-558. doi:10.1016/j.jpsychires.2022.09.052