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

Abstract

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.

Immunogenetic Epidemiology of Multiple Sclerosis in 14 Continental Western European Countries

“…HLA profiles for MS were derived as described previously for Parkinson's disease and dementia 26 . Briefly, the prevalence of MS in a country was computed as the fraction of total country population and was expressed as a percentage.…”

“…Briefly, the prevalence of MS in a country was computed as the fraction of total country population and was expressed as a percentage. MS prevalences were natural-log transformed [23][24][25][26] and the Pearson correlation coefficient, r, between MS prevalence and the population frequency of each one of the 127 HLA alleles above calculated and Fisher z−transformed 33 to normalize its distribution:…”

“…Here we take an alternative immunogenetic epidemiology approach that takes advantage of the population heterogeneity of HLA and permits identification of a high-resolution population level HLA profile with regard to disease prevalence. Using this approach, we [23][24][25][26] and others 13 have identified HLA alleles that are negatively associated with disease prevalence (i.e., protective alleles) as well as HLA alleles that are positively associated with disease prevalence (i.e., susceptibility alleles). In light of HLA's involvement in pathogen elimination and autoimmunity, we presume that protective alleles facilitate pathogen elimination and that susceptibility alleles promote autoimmunity.…”

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“…Burgeoning evidence has demonstrated HLA associations with dementia and Parkinson's disease [1][2][3]9,[17][18][19][20][21] . Using an across-countries population immunogenetic epidemiological approach 22 , we initially investigated associations between the population frequency of HLA Class II DRB1 alleles and dementia across 14 countries in Continental Western Europe 1,2 .…”

“…This approach permits identification of an HLA profile wherein HLA alleles may presumably be characterized as protective alleles (negatively correlated with population prevalence of a disease) or susceptibility alleles (positively correlated with the population prevalence of a disease). With respect to HLA Class II DRB1 alleles, we recently found that the HLA profiles of dementia and Parkinson's disease for a small number of HLA alleles are very similar, suggesting that similar immunogenetic mechanisms may underlie the pathogenesis of these conditions 3 . Here we extend that line of research to evaluate the correspondence in the association of the population frequency of 127 HLA Class I and Class II alleles and the population prevalence of dementia and Parkinson's disease which will permit characterization of HLA-disease profiles.…”