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APOE epsilon‐4 allele and cytokine production in Alzheimer's disease
Author(s) -
Olgiati Paolo,
Politis Antonis,
Malitas Petros,
Albani Diego,
Dusi Sabrina,
Polito Letizia,
De Mauro Stefania,
Zisaki Aikaterini,
Piperi Christina,
Stamouli Evangelia,
Mailis Antonis,
Batelli Sara,
Forloni Gianluigi,
De Ronchi Diana,
Kalofoutis Anastasios,
Liappas Ioannis,
Serretti Alessandro
Publication year - 2010
Publication title -
international journal of geriatric psychiatry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 129
eISSN - 1099-1166
pISSN - 0885-6230
DOI - 10.1002/gps.2344
Subject(s) - apolipoprotein e , allele , cytokine , immunology , peripheral blood mononuclear cell , dementia , tumor necrosis factor alpha , disease , alzheimer's disease , pathophysiology , genotype , interleukin , medicine , biology , genetics , gene , in vitro
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‐1 β 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‐1 β . 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‐1 β 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. Copyright © 2009 John Wiley & Sons, Ltd.