Tri-Allelic Human Leukocyte Antigen (HLA) Protection Against Dementia.

Human Leukocyte Antigen (HLA) Class II DRB113:02 has recently been found to protect against dementia in Continental Western Europe. Here we extend those findings by evaluating the association between the population frequency of two additional Class II HLA alleles - DRB101:01 and DRB115:01 - alone and in combination with DRB113:02, on dementia prevalence in Continental Western Europe. Results indicated that the prevalence of dementia in 14 Continental Western European (CWE) countries significantly decreased exponentially with increasing frequency of any of the three alleles alone and in combination (P's < 0.001). When combined, the population frequency of the three alleles accounted for 67% of the variance in dementia prevalence. The combined frequency of DRB101:01, DRB113:02, and DRB1*15:01 was also significantly associated with dementia prevalence in those aged 65 years and older (P = 0.004) and with a change in dementia prevalence between 1990 and 2016 (P = 0.006). These findings, which document the protective effects of three common Class II HLA alleles on dementia prevalence in CWE, are discussed in terms of the role of HLA class II genes in pathogen elimination. More specifically, we hypothesize that dementia prevalence is higher for countries in which the population frequency of these protective alleles is low, prohibiting the successful elimination of pathogens that may play a causal role in dementia.