Shared Human Leukocyte Antigen (HLA) Coverage in dementia and Parkinson's disease

Dementia and Parkinson's disease are the two most common age-related neurodegenerative conditions. Recent studies have identified Human Leukocyte Antigen (HLA) Class II DRB1 alleles that are protective or neutral with respect to dementia. Here we extend those findings to evaluate the association of the population frequency of HLA DRB1 alleles with the prevalence of dementia and Parkinson's disease in14 Continental Western European countries. Nine HLA DRB1 alleles were identified including four that are protective against dementia (DRB1*01:01, DRB1*04:01, DRB1*13:02, DRB1*15:01), three that are neutral (DRB1*03:01, DRB1*07:01, DRB1*08:01), and two susceptibility alleles (DRB1*11:01, DRB1*04:05). Results demonstrated that the population prevalence's of dementia and Parkinson's disease are highly correlated and that the association between the nine DRB1 alleles above and the population prevalence of dementia is highly overlapping with that of Parkinson's disease. These findings suggest a common HLA Class II DRB1 profile. Given the diverse role of HLA Class II alleles in protection from foreign antigens, autoimmunity, and, possibly, neuroprotection, the shared HLA profile between dementia and Parkinson's disease indicates that common immunogenetic mechanisms underlie the pathogenesis and manifestation of these diseases.