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


CONCLUSIONS
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.
Olgiati
Paolo
P
Institute of Psychiatry, University of Bologna, Bologna, Italy.
Politis
Antonis
A
Malitas
Petros
P
Albani
Diego
D
Dusi
Sabrina
S
Polito
Letizia
L
De Mauro
Stefania
S
Zisaki
Aikaterini
A
Piperi
Christina
C
Stamouli
Evangelia
E
Mailis
Antonis
A
Batelli
Sara
S
Forloni
Gianluigi
G
De Ronchi
Diana
D
Kalofoutis
Anastasios
A
Liappas
Ioannis
I
Serretti
Alessandro
A
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000523:psychology; D001057:Apolipoproteins E / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D011569:Psychiatric Status Rating Scales; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D001057:Apolipoproteins E; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha