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Cited by 14Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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

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Huang, Jinghan, Stein, Thor D., Wang, Yixuan, Ang, Ting Fang Alvin, Tao, Qiushan, Lunetta, Kathryn L., Massaro, Joseph, Akhter‐Khan, Samia C. +6 more·2023·Alzheimer's & Dementia
DOI 10.1002/alz.12851PMC PMC10182187
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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.

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  • C-reactive protein (CRP) and MCP-1 interact with APOE ε4 versus APOE ε2 in an opposite direction to impact Alzheimer's disease risk.

    “our recent studies have shown that several proinflammatory proteins including C‐reactive protein (CRP) and MCP‐1 interact with APOE ε4 versus APOE ε2 in an opposite direction to impact AD risk [3, 4].”

    From Blood PCSK9 Impacts Alzheimer's Disease Risk in an <i>APOE</i> Genotype‐Dependent Manner: A Prospective Cohort Study (2026) · cites this paper as [4]

    The Results (Characteristics of the FHS population; page not provided) report that MCP-1 interacts with APOE ε4 and APOE ε2 in opposite directions for AD risk. The paper says CRP increases AD risk in APOE ε4 carriers, but does not establish an opposite-direction CRP interaction with APOE ε2. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Some proinflammatory proteins in blood impact APOE genotypes differently for AD risk.

    “As some proinflammatory proteins in blood impact APOE genotypes differently for AD risk [4, 20]”

    From Blood PCSK9 Impacts Alzheimer's Disease Risk in an <i>APOE</i> Genotype‐Dependent Manner: A Prospective Cohort Study (2026) · cites this paper as [4]

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Cited by

Sorted by citations

Authors
Huang, J., Stein, T. D., Wang, Y., Ang, T. F. A., Tao, Q., Lunetta, K. L., Massaro, J., Akhter‐Khan, S. C., Mez, J., Au, R., Farrer, L. A., Zhang, X., Qiu, W. Q., & Initiative, F. T. A. D. N.
Affiliations
Boston University (US)
Corresponding author
Qiu, Wei Qiao
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2022-11-17
Volume
19
Issue
5
Pages
1925-1937
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1002/alz.12851
PMC
PMC10182187
OpenAlex
W4309261576
Cited by
14
References
14
Citations by year
2026: 2 · 2025: 7 · 2024: 3 · 2023: 2
FWCI
1.86
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Alzheimer s & Dementia (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
  • National Institute on Aging (U19‐AG068753, RF1‐AG057519, R01‐AG048927)
  • National Institutes of Health (U01 AG024904)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, MCP-1
MeSH terms
Alzheimer Disease, Apolipoproteins E, Genotype, Humans, Chemokine CCL2, Apolipoprotein E4, HLA-DRB1 Chains

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