TY - JOUR
T1 - Acetyl Cholinesterase Inhibitors and Cell-Derived Peripheral Inflammatory Cytokines in Early Stages of Alzheimer's Disease
AU - Kokras, Nikolaos
AU - Stamouli, Evangelia
AU - Sotiropoulos, Ioannis
AU - Katirtzoglou, Everina A.
AU - Siarkos, Kostas T.
AU - Dalagiorgou, Georgia
AU - Alexandraki, Krystallenia I.
AU - Coulocheri, Stavroula
AU - Piperi, Christina
AU - Politis, Antonios M.
N1 - Funding Information:
Funding was received from a program co-financed by the European Social Fund and the Greek State (GSRT LS5-3808). N.K. has received honoraria and travel support from Janssen-Cilag, Lundbeck, Sanofi-Aventis, Medochemie Generics, and Elpen S.A. None of those is relevant to this study. The authors declare no conflicts of interest.
Publisher Copyright:
Copyright © Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Background Clinical and preclinical studies firmly support the involvement of the inflammation in the pathogenesis of Alzheimer's disease (AD). Despite acetylcholinesterase inhibitors (AChEI) being widely used in AD patients, there is no conclusive evidence about their impact on the inflammatory response. Methods This study investigates peripheral proinflammatory cytokines (interferon gamma [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukins 1β [IL-1β] and 6 [IL-6]) by firstly comparing peripheral blood mononuclear cell (PBMC)-derived secretion in drug-naïve and AChEI-treated AD patients versus healthy controls. A subset of those drug-naïve AD patients, who were prescribed the AChEI donepezil, was followed-up for 6 months to investigate if donepezil suppresses proinflammatory cell-derived cytokine secretion. Results Patients with AD showed higher levels of PBMC-derived proinflammatory cytokines (IFN-γ, TNF-α, IL-1β, and IL-6) in comparison with healthy controls. On reexamination, previously drug-naïve AD patients who received donepezil treatment for 6 months displayed a decrease in cell-derived IFN-γ, TNF-α, IL-1β, and IL-6. Conclusions Proinflammatory PBMC-derived cytokines were increased in patients with AD in comparison with healthy controls and donepezil-reduced proinflammatory cytokines when examining drug-naïve AD patients before and after AChEI treatment.
AB - Background Clinical and preclinical studies firmly support the involvement of the inflammation in the pathogenesis of Alzheimer's disease (AD). Despite acetylcholinesterase inhibitors (AChEI) being widely used in AD patients, there is no conclusive evidence about their impact on the inflammatory response. Methods This study investigates peripheral proinflammatory cytokines (interferon gamma [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukins 1β [IL-1β] and 6 [IL-6]) by firstly comparing peripheral blood mononuclear cell (PBMC)-derived secretion in drug-naïve and AChEI-treated AD patients versus healthy controls. A subset of those drug-naïve AD patients, who were prescribed the AChEI donepezil, was followed-up for 6 months to investigate if donepezil suppresses proinflammatory cell-derived cytokine secretion. Results Patients with AD showed higher levels of PBMC-derived proinflammatory cytokines (IFN-γ, TNF-α, IL-1β, and IL-6) in comparison with healthy controls. On reexamination, previously drug-naïve AD patients who received donepezil treatment for 6 months displayed a decrease in cell-derived IFN-γ, TNF-α, IL-1β, and IL-6. Conclusions Proinflammatory PBMC-derived cytokines were increased in patients with AD in comparison with healthy controls and donepezil-reduced proinflammatory cytokines when examining drug-naïve AD patients before and after AChEI treatment.
KW - Alzheimer's disease
KW - anticholinesterase inhibitors
KW - cytokines
KW - donepezil
KW - inflammation
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U2 - 10.1097/JCP.0000000000000840
DO - 10.1097/JCP.0000000000000840
M3 - Article
C2 - 29420357
AN - SCOPUS:85043463138
SN - 0271-0749
VL - 38
SP - 138
EP - 143
JO - Journal of clinical psychopharmacology
JF - Journal of clinical psychopharmacology
IS - 2
ER -