APOE epsilon-4 allele and cytokine production in Alzheimer's disease

Int J Geriatr Psychiatry. 2010 Apr;25(4):338-44. doi: 10.1002/gps.2344.


Objective: The APOE epsilon-4 allele has consistently emerged as a susceptibility factor for Alzheimer's disease (AD). Pro-inflammatory cytokines are detectable at abnormal levels in AD, and are thought to play a pathophysiological role. Animal studies have shown dose-dependent correlations between the number of APOE epsilon-4 alleles and the levels of pro-inflammatory cytokines. The aims of this study were to investigate the influence of APOE genotypes on TNF-alpha, IL-6, and IL-1beta secreted by peripheral blood mononuclear cells (PBMC) from human patients with AD and to analyze the correlation between cytokine production and AD clinical features.

Methods: Outpatients with AD (n = 40) were clinically evaluated for cognitive decline (MMSE) and psychiatric symptoms (Cornell Scale for Depression in Dementia; Neuropsychiatric Inventory) and genotyped for APOE variants. PBMCs were isolated from the donors and used to assess spontaneous and PMA-stimulated secretion of TNF-alpha, IL-6, and IL-1beta. Cytokine production was determined by immuno-enzymatic assays (ELISA).

Results: In comparison with their counterparts without APOE4, patients with at least one copy of the APOE epsilon-4 allele showed higher spontaneous (p = 0.037) and PMA-induced (p = 0.039) production of IL-1beta after controlling for clinical variables. Significant correlations were reported between NPI scores (psychotic symptoms) and IL-6 production.

Conclusion: These preliminary findings suggest the involvement of inflammatory response in the pathogenic effect of the APOE epsilon-4 allele in AD, although their replication in larger samples is mandatory. The modest correlations between pro-inflammatory cytokines released at peripheral level and AD features emphasizes the need for further research to elucidate the role of neuroinflammation in pathophysiology of AD.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / psychology
  • Apolipoproteins E / genetics*
  • Cognition Disorders / diagnosis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genotype
  • Humans
  • Interleukin-1beta / metabolism*
  • Interleukin-6 / metabolism*
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Psychiatric Status Rating Scales
  • Tumor Necrosis Factor-alpha / metabolism*


  • Apolipoproteins E
  • Interleukin-1beta
  • Interleukin-6
  • Tumor Necrosis Factor-alpha