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

Area of Science:

• Immunogenetics
• Neuroepidemiology

Background:

• Human Leukocyte Antigen (HLA) Class II DRB1*13:02 has shown protective effects against dementia.
• The role of other common HLA Class II alleles in dementia prevalence remains under investigation.

Purpose of the Study:

• To evaluate the association between population frequencies of HLA Class II alleles DRB1*01:01 and DRB1*15:01, alone and with DRB1*13:02, and dementia prevalence.
• To investigate the combined effect of these three HLA alleles on dementia prevalence across Continental Western Europe.

Main Methods:

• Analysis of population frequencies of HLA Class II alleles DRB1*01:01, DRB1*13:02, and DRB1*15:01 in 14 Continental Western European countries.
• Statistical assessment of the correlation between allele frequencies and dementia prevalence, including age-specific and temporal changes.

Main Results:

• Dementia prevalence decreased exponentially with increasing frequencies of DRB1*01:01, DRB1*13:02, and DRB1*15:01, both individually and combined (P < 0.001).
• The combined frequency of these three alleles explained 67% of the variance in dementia prevalence.
• Significant associations were found with dementia prevalence in individuals aged 65+ (P = 0.004) and changes in prevalence between 1990-2016 (P = 0.006).

Conclusions:

• Three common Class II HLA alleles (DRB1*01:01, DRB1*13:02, DRB1*15:01) demonstrate a protective effect against dementia in Continental Western Europe.
• Lower population frequencies of these protective alleles may be linked to higher dementia prevalence, potentially due to impaired pathogen elimination.
• HLA Class II genes play a significant role in pathogen defense, influencing dementia risk.