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

Paolo Olgiati, Antonis Politis, Petros Malitas, Diego Albani, Sabrina Dusi, Letizia Polito, Stefania De Mauro, Aikaterini Zisaki, Christina Piperi, Evangelia Stamouli, Antonis Mailis, Sara Batelli, Gianluigi Forloni, Diana De Ronchi, Anastasios Kalofoutis, Ioannis Liappas, Alessandro Serretti

Research output: Contribution to journalArticle

Abstract

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-α, IL-6, and IL-1β 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-α, IL-6, and IL-1β. Cytokine production was determined by immunoenzymatic 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-1β 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.

Original languageEnglish (US)
Pages (from-to)338-344
Number of pages7
JournalInternational Journal of Geriatric Psychiatry
Volume25
Issue number4
DOIs
Publication statusPublished - Apr 2010
Externally publishedYes

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Keywords

  • Alzheimer
  • APOE
  • Cytokine
  • In vivo
  • Inflammatory response

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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