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. 2020 Sep 22;5(3):45-54.
doi: 10.29245/2572.942x/2020/3.1275.

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

Lisa M James  1   2   3 , Apostolos P Georgopoulos  1   2   3   4
Affiliations

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

Lisa M James et al. J Neurol Neuromedicine. .

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.

Keywords: Dementia; Genetics; Human Leukocyte Antigen; Immunity; Parkinson’s Disease.

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Conflict of interest statement

Conflicts of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1.
Figure 1.
Dementia prevalence in 14 CWE countries is plotted against the prevalence of Parkinson’s disease. See text for details.
Figure 2.
Figure 2.
Illustration of the different effects of each protective allele on the natural log of dementia prevalence as evidenced by the varying steepness of the slopes.
Figure 3.
Figure 3.
Illustration of the different effects of each protective allele on the natural log of Parkinson’s disease prevalence as evidenced by the varying steepness of the slopes.
Figure 4.
Figure 4.
The natural log of dementia prevalence is plotted against the sum of the frequencies of the four protective alleles (DRB1*01:01, DRB1*04:01, DRB1*13:02, DRB1*15:01). See text for details.
Figure 5.
Figure 5.
The natural log of Parkinson’s disease prevalence is plotted against the sum of the frequencies of the four protective alleles (DRB1*01:01, DRB1*04:01, DRB1*13:02, DRB1*15:01). See text for details.
Figure 6.
Figure 6.
The natural log of dementia prevalence is plotted against the frequency of the three neutral alleles; there is no significant association. See text for details.
Figure 7.
Figure 7.
The natural log of Parkinson’s disease prevalence is plotted against the frequency of the three neutral alleles; there is no significant association. See text for details.
Figure 8.
Figure 8.
The natural log of dementia prevalence is plotted against the sum of the frequencies of the three neutral (DRB1*03:01, DRB1*07:01, DRB1*08:01); there is no significant association. See text for details.
Figure 9.
Figure 9.
The natural log of Parkinson’s disease prevalence is plotted against the sum of the frequencies of the three neutral (DRB1*03:01, DRB1*07:01, DRB1*08:01); there is no significant association. See text for details.
Figure 10.
Figure 10.
Illustration of the different effects of each predisposing allele on the natural log of dementia prevalence as evidenced by the varying steepness of the slopes.
Figure 11.
Figure 11.
Illustration of the different effects of each predisposing allele on the natural log of Parkinson’s disease prevalence as evidenced by the varying steepness of the slopes.
Figure 12.
Figure 12.
The natural log of dementia prevalence is plotted against the sum of the frequencies of the two predisposing alleles (DRB1*04:05, DRB1*11:01). See text for details.
Figure 13.
Figure 13.
The natural log of Parkinson’s disease prevalence is plotted against the sum of the frequencies of the two predisposing alleles (DRB1*04:05, DRB1*11:01). See text for details.
Figure 14.
Figure 14.
The HLA profile of Parkinson’s disease is plotted against the HLA profile of dementia; data from Table 4. Blue, protective alleles; black, neutral alleles; red, predisposing alleles.
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