KIR2DS2/KIR2DL2/HLA-C1 Haplotype Is Associated with Alzheimer's Disease: Implication for the Role of Herpesvirus Infections

J Alzheimers Dis. 2019;67(4):1379-1389. doi: 10.3233/JAD-180777.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, where neuroinflammation and immune cells are key pathological factors. Recently, it was suggested a possible association between AD and human herpesvirus 6 (HHV-6) infection. Since we recently observed that multiple sclerosis patients with KIR2DL2 expression on natural killer (NK) cells are more susceptible to herpesvirus infection, we tested the possible implication of KIR/HLA genetic for HHV-6A infection. We identified, for the first time, a possible implication of a specific KIR/HLA subset in AD. The combination KIR2DS2/KIR2DL2/C1 correlated with a lower MMSEDi score, representative of a severe AD status and an increased susceptibility to HHV-6A infection. Therefore, the results seem to converge on the hypothesis that herpesvirus infection might play a role in AD. If this hypothesis finds experimental confirmation, a new therapeutic strategy, modulating KIR2DL2 expression on NK cells, for AD might be envisaged.

Keywords: Alzheimer’s disease; HHV-6A; KIR; NK cell; herpesvirus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / virology
  • Apolipoproteins E / genetics
  • Female
  • Gene Expression
  • Gene Expression Profiling / methods
  • Haplotypes / genetics*
  • Herpesviridae Infections* / genetics
  • Herpesviridae Infections* / virology
  • Herpesvirus 6, Human / isolation & purification*
  • Humans
  • Killer Cells, Natural / metabolism
  • Male
  • Mental Status and Dementia Tests
  • Receptors, KIR / genetics*
  • Receptors, KIR2DL2 / genetics*

Substances

  • Apolipoproteins E
  • KIR2DL2 protein, human
  • KIR2DS2 protein, human
  • Receptors, KIR
  • Receptors, KIR2DL2