The Human Leukocyte Antigen (HLA) DRB1*13:02 Allele Protects against Dementia in Continental Western Europe

Abstract

Human Leukocyte Antigen (HLA) Class II DRB1*13 alleles have recently been found to protect against age-related brain deterioration, even in the presence of apolipoprotein E4 (apoE4),^1,2 suggesting a possible protection against dementia. Here we evaluated the association between the population frequency of common DRB1*13 alleles and the prevalence of dementia in Continental Western Europe. Prevalence of dementia in Continental Western Europe was derived from published reports on dementia frequency from the Global Burden of Disease Study 2016 and population totals obtained from the Population Reference Bureau. DRB1*13:01 and DRB1*13:02 allele frequencies were obtained from a publicly available database (allelefrequency.net) and apolipoprotein E was obtained from published reports on the world distribution of apoE4. The prevalence of dementia in 14 Continental Western European (CWE) countries, where life expectancy is practically identical, significantly decreases exponentially with increasing frequency of DRB1*13:02 (R² = 0.452, P = 0.008), even when adjusted for the prevalence of apolipoprotein E4 allele, a known risk factor for Alzheimer's disease. This finding documents the protective effect of DRB1*13:02 on dementia prevalence in CWE. Since the function of HLA class II genes is to aid in the elimination of pathogens by enabling the production of antibodies against their antigens in specific immunity, the protective effect of DRB1*13:02 points to the presence of persistent harmful antigens as causal factors in development of dementia, antigens specific to DRB1*13:02 that could not be eliminated in its absence.

Keywords: Apolipoprotein E; Dementia; Human Leukocyte Antigen; Persistent Antigens.

Figure 1:

Dementia prevalence (5) is plotted against DRB1*13:02 frequency with countries identified by names (A) or national flags (B). (See text for details.)

Figure 2:

Illustration of the quantitative effect of DRB1*13:02 frequency on dementia prevalence, based on the fitted exponential fit of equation 2 (see text). An increase of 100% (doubling) of the DRB1*13:02 frequency results in 31% reduction in dementia prevalence.