Blood levels of MCP-1 modulate the genetic risks of Alzheimer's disease mediated by HLA-DRB1 and APOE for Alzheimer's disease

Alzheimers Dement. 2023 May;19(5):1925-1937. doi: 10.1002/alz.12851. Epub 2022 Nov 17.

Abstract

Introduction: C-Reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) are both implicated in the peripheral proinflammatory cascade and blood-brain barrier (BBB) disruption. Since the blood CRP level increases Alzheimer's disease (AD) risk depending on the apolipoprotein E (APOE) genotype, we hypothesized that the blood MCP-1 level exerts different effects on the AD risk depending on the genotypes.

Methods: Using multiple regression analyses, data from the Framingham Heart Study (n = 2884) and Alzheimer's Disease Neuroimaging Initiative study (n = 231) were analyzed.

Results: An elevated blood MCP-1 level was associated with AD risk in major histocompatibility complex, Class II, DR beta 1 (HLA-DRB1) rs9271192-AC/CC (hazard ratio [HR] = 3.07, 95% confidence interval [CI] = 1.50-6.28, p = 0.002) and in APOE ε4 carriers (HR = 3.22, 95% CI = 1.59-6.53, p = 0.001). In contrast, among HLA-DRB1 rs9271192-AA and APOE ε4 noncarriers, blood MCP-1 levels were not associated with these phenotypes.

Discussion: Since HLA-DRB1 and APOE are expressed in the BBB, blood MCP-1 released in the peripheral inflammatory cascade may function as a mediator of the effects of HLA-DRB1 rs9271192-AC/CC and APOE ε4 genotypes on AD pathogenesis in the brain via the BBB pathways.

Keywords: Alzheimer's disease; MCP-1; blood; genotypes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alzheimer Disease* / blood
  • Alzheimer Disease* / genetics
  • Apolipoprotein E4 / genetics
  • Apolipoproteins E* / genetics
  • Chemokine CCL2* / blood
  • Genotype
  • HLA-DRB1 Chains* / genetics
  • Humans

Substances

  • Apolipoprotein E4
  • Apolipoproteins E
  • Chemokine CCL2
  • HLA-DRB1 Chains