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

作者：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^*

来源：International Journal of Geriatric Psychiatry, 2010, 25(4): 338-344.

DOI：10.1002/gps.2344

• Alzheimer
• APOE
• cytokine
• inflammatory response
• in vivo

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-1 beta 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-16, and IL-1 beta. 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-1 beta 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.

• 出版日期2010-4