{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T20:29:20Z","timestamp":1773865760354,"version":"3.50.1"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Clin Psychopharmacol"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Clinical and preclinical studies firmly support the involvement of the inflammation in the pathogenesis of Alzheimer\u2019s disease (AD). Despite acetylcholinesterase inhibitors (AChEI) being widely used in AD patients, there is no conclusive evidence about their impact on the inflammatory response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study investigates peripheral proinflammatory cytokines (interferon gamma [IFN-\u03b3], tumor necrosis factor alpha [TNF-\u03b1], and interleukins 1\u03b2 [IL-1\u03b2] and 6 [IL-6]) by firstly comparing peripheral blood mononuclear cell (PBMC)\u2013derived secretion in drug-na\u00efve and AChEI-treated AD patients versus healthy controls. A subset of those drug-na\u00efve AD patients, who were prescribed the AChEI donepezil, was followed-up for 6 months to investigate if donepezil suppresses proinflammatory cell-derived cytokine secretion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with AD showed higher levels of PBMC-derived proinflammatory cytokines (IFN-\u03b3, TNF-\u03b1, IL-1\u03b2, and IL-6) in comparison with healthy controls. On reexamination, previously drug-na\u00efve AD patients who received donepezil treatment for 6 months displayed a decrease in cell-derived IFN-\u03b3, TNF-\u03b1, IL-1\u03b2, and IL-6.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Proinflammatory PBMC-derived cytokines were increased in patients with AD in comparison with healthy controls and donepezil-reduced proinflammatory cytokines when examining drug-na\u00efve AD patients before and after AChEI treatment.<\/jats:p><\/jats:sec>","DOI":"10.1097\/jcp.0000000000000840","type":"journal-article","created":{"date-parts":[[2018,2,8]],"date-time":"2018-02-08T15:33:56Z","timestamp":1518104036000},"page":"138-143","source":"Crossref","is-referenced-by-count":26,"title":["Acetyl Cholinesterase Inhibitors and Cell-Derived Peripheral Inflammatory Cytokines in Early Stages of Alzheimer's Disease"],"prefix":"10.1097","volume":"38","author":[{"given":"Nikolaos","family":"Kokras","sequence":"first","affiliation":[{"name":"From the *First Department of Psychiatry, Eginitio Hospital, \u2020Department of Pharmacology, and \u2021Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Greece; \u00a7Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, & ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga, Portugal; and \u2225Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Greece."}]},{"given":"Evangelia","family":"Stamouli","sequence":"additional","affiliation":[{"name":"From the *First Department of Psychiatry, Eginitio Hospital, \u2020Department of Pharmacology, and \u2021Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Greece; \u00a7Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, & ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga, Portugal; and \u2225Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Greece."}]},{"given":"Ioannis","family":"Sotiropoulos","sequence":"additional","affiliation":[{"name":"From the *First Department of Psychiatry, Eginitio Hospital, \u2020Department of Pharmacology, and \u2021Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Greece; \u00a7Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, & ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga, Portugal; and \u2225Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Greece."}]},{"given":"Everina A.","family":"Katirtzoglou","sequence":"additional","affiliation":[{"name":"From the *First Department of Psychiatry, Eginitio Hospital, \u2020Department of Pharmacology, and \u2021Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Greece; \u00a7Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, & ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga, Portugal; and \u2225Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Greece."}]},{"given":"Kostas T.","family":"Siarkos","sequence":"additional","affiliation":[{"name":"From the *First Department of Psychiatry, Eginitio Hospital, \u2020Department of Pharmacology, and \u2021Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Greece; \u00a7Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, & ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga, Portugal; and \u2225Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Greece."}]},{"given":"Georgia","family":"Dalagiorgou","sequence":"additional","affiliation":[{"name":"From the *First Department of Psychiatry, Eginitio Hospital, \u2020Department of Pharmacology, and \u2021Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Greece; \u00a7Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, & ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga, Portugal; and \u2225Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Greece."}]},{"given":"Krystallenia I.","family":"Alexandraki","sequence":"additional","affiliation":[{"name":"From the *First Department of Psychiatry, Eginitio Hospital, \u2020Department of Pharmacology, and \u2021Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Greece; \u00a7Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, & ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga, Portugal; and \u2225Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Greece."}]},{"given":"Stavroula","family":"Coulocheri","sequence":"additional","affiliation":[{"name":"From the *First Department of Psychiatry, Eginitio Hospital, \u2020Department of Pharmacology, and \u2021Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Greece; \u00a7Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, & ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga, Portugal; and \u2225Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Greece."}]},{"given":"Christina","family":"Piperi","sequence":"additional","affiliation":[{"name":"From the *First Department of Psychiatry, Eginitio Hospital, \u2020Department of Pharmacology, and \u2021Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Greece; \u00a7Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, & ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga, Portugal; and \u2225Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Greece."}]},{"given":"Antonios M.","family":"Politis","sequence":"additional","affiliation":[{"name":"From the *First Department of Psychiatry, Eginitio Hospital, \u2020Department of Pharmacology, and \u2021Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Greece; \u00a7Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, & ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga, Portugal; and \u2225Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Greece."}]}],"member":"276","reference":[{"key":"bib1-20230927","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1017\/S1041610208007382","article-title":"Developing new treatments for Alzheimer's disease: the who, what, when, and how of biomarker-guided therapies","volume":"20","year":"2008","journal-title":"Int Psychogeriatr"},{"key":"bib2-20230927","first-page":"E3755","article-title":"Tau protein is essential for stress-induced brain pathology","volume":"113","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"bib3-20230927","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.neubiorev.2008.05.007","article-title":"Stress and glucocorticoid footprints in the brain-the path from depression to Alzheimer's disease","volume":"32","year":"2008","journal-title":"Neurosci Biobehav Rev"},{"key":"bib4-20230927","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jalz.2016.02.010","article-title":"Neuroinflammation in Alzheimer's disease: current evidence and future directions","volume":"12","year":"2016","journal-title":"Alzheimers Dement"},{"key":"bib5-20230927","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1080\/02646830500382037","article-title":"Clinical aspects of inflammation in Alzheimer's disease","volume":"17","year":"2005","journal-title":"Int Rev Psychiatry"},{"key":"bib6-20230927","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1159\/000354228","article-title":"Neuroinflammatory phenotypes and their roles in Alzheimer's disease","volume":"13","year":"2014","journal-title":"Neurodegener Dis"},{"key":"bib7-20230927","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1080\/00207450701392068","article-title":"Cytokines in Alzheimer's disease and vascular dementia","volume":"118","year":"2008","journal-title":"Int J Neurosci"},{"key":"bib8-20230927","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1136\/jnnp.74.6.788","article-title":"Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer's disease","volume":"74","year":"2003","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"bib9-20230927","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0165-5728(94)90108-2","article-title":"Correlation of cytokine secretion by mononuclear cells of Alzheimer patients and their disease stage","volume":"52","year":"1994","journal-title":"J Neuroimmunol"},{"key":"bib10-20230927","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1017\/S1041610208008107","article-title":"IL-6 release by LPS-stimulated peripheral blood mononuclear cells as a potential biomarker in Alzheimer's disease","volume":"21","year":"2009","journal-title":"Int Psychogeriatr"},{"key":"bib11-20230927","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.neuropharm.2005.10.013","article-title":"Anti-inflammatory properties of cholinergic up-regulation: a new role for acetylcholinesterase inhibitors","volume":"50","year":"2006","journal-title":"Neuropharmacology"},{"key":"bib12-20230927","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.neuropharm.2013.06.023","article-title":"The anti-inflammatory effect of donepezil on experimental autoimmune encephalomyelitis in C57 BL\/6 mice","volume":"73","year":"2013","journal-title":"Neuropharmacology"},{"key":"bib13-20230927","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1093\/ajh\/hpv017","article-title":"Acetylcholinesterase inhibition attenuates the development of hypertension and inflammation in spontaneously hypertensive rats","volume":"28","year":"2015","journal-title":"Am J Hypertens"},{"key":"bib14-20230927","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1002\/gps.3966","article-title":"Blood pro-inflammatory cytokines in Alzheimer's disease in relation to the use of acetylcholinesterase inhibitors","volume":"28","year":"2013","journal-title":"Int J Geriatr Psychiatry"},{"key":"bib15-20230927","doi-asserted-by":"crossref","first-page":"154","DOI":"10.2174\/1567205011310020005","article-title":"Effects of SORL1 gene on Alzheimer's disease. 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