{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:41:31Z","timestamp":1789497691478,"version":"build-2803163510"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T00:00:00Z","timestamp":1427846400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["81373384"],"award-info":[{"award-number":["81373384"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100014857","name":"NSFC-Guangdong Joint Fund","doi-asserted-by":"crossref","award":["U1032006"],"award-info":[{"award-number":["U1032006"]}],"id":[{"id":"10.13039\/501100014857","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroscience"],"published-print":{"date-parts":[[2015,4]]},"DOI":"10.1016\/j.neuroscience.2015.01.058","type":"journal-article","created":{"date-parts":[[2015,2,4]],"date-time":"2015-02-04T17:47:48Z","timestamp":1423072068000},"page":"530-542","source":"Crossref","is-referenced-by-count":89,"special_numbering":"C","title":["Donepezil improves learning and memory deficits in APP\/PS1 mice by inhibition of microglial activation"],"prefix":"10.1016","volume":"290","author":[{"given":"H.B.","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.F.","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.G.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.M.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.T.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.K.","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.P.","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.neuroscience.2015.01.058_b0005","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1210\/mend-4-8-1125","article-title":"Insulin-degrading enzyme: stable expression of the human complementary DNA, characterization of its protein product, and chromosomal mapping of the human and mouse genes","volume":"4","author":"Affholter","year":"1990","journal-title":"Mol Endocrinol"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0010","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1212\/01.wnl.0000261920.03297.64","article-title":"Cholinesterase inhibitors reduce cortical Abeta in dementia with Lewy bodies","volume":"68","author":"Ballard","year":"2007","journal-title":"Neurology"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0015","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1001\/jamaneurol.2013.5847","article-title":"Amyloid-beta and tau: the trigger and bullet in Alzheimer disease pathogenesis","volume":"71","author":"Bloom","year":"2014","journal-title":"JAMA Neurol"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0020","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/35013070","article-title":"Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin","volume":"405","author":"Borovikova","year":"2000","journal-title":"Nature"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0025","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1212\/WNL.0b013e3181a18691","article-title":"Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort","volume":"72","author":"Breitner","year":"2009","journal-title":"Neurology"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0030","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S0002-9440(10)63822-9","article-title":"Reduced hippocampal insulin-degrading enzyme in late-onset Alzheimer\u2019s disease is associated with the apolipoprotein E-epsilon4 allele","volume":"162","author":"Cook","year":"2003","journal-title":"Am J Pathol"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0035","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jalz.2011.03.012","article-title":"Nonsteroidal anti-inflammatory drug use and the risk of cognitive impairment and Alzheimer\u2019s disease","volume":"8","author":"Cote","year":"2012","journal-title":"Alzheimers Dement"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0040","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/alzrt215","article-title":"Neuroprotective effects of donepezil against cholinergic depletion","volume":"5","author":"Cutuli","year":"2013","journal-title":"Alzheimers Res Ther"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0045","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s00213-013-3152-3","article-title":"Effects of sub-chronic donepezil on brain Abeta and cognition in a mouse model of Alzheimer\u2019s disease","volume":"230","author":"Easton","year":"2013","journal-title":"Psychopharmacology"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0050","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1016\/S0002-9440(10)63229-4","article-title":"Partial loss-of-function mutations in insulin-degrading enzyme that induce diabetes also impair degradation of amyloid beta-protein","volume":"164","author":"Farris","year":"2004","journal-title":"Am J Pathol"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0055","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/BF00227813","article-title":"Ultrastructure of the microglia that phagocytose amyloid and the microglia that produce beta-amyloid fibrils","volume":"84","author":"Frackowiak","year":"1992","journal-title":"Acta Neuropathol"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0060","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.nbd.2006.08.017","article-title":"Characterization of amyloid deposition in the APPswe\/PS1dE9 mouse model of Alzheimer disease","volume":"24","author":"Garcia-Alloza","year":"2006","journal-title":"Neurobiol Dis"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0065","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.brainresbull.2004.06.008","article-title":"Galantamine and nicotine have a synergistic effect on inhibition of microglial activation induced by HIV-1 gp120","volume":"64","author":"Giunta","year":"2004","journal-title":"Brain Res Bull"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0070","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1212\/01.wnl.0000265223.25679.2a","article-title":"Does NSAID use modify cognitive trajectories in the elderly? The Cache County study","volume":"69","author":"Hayden","year":"2007","journal-title":"Neurology"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0075","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1083\/jcb.200705042","article-title":"Deletion of tumor necrosis factor death receptor inhibits amyloid beta generation and prevents learning and memory deficits in Alzheimer\u2019s mice","volume":"178","author":"He","year":"2007","journal-title":"J Cell Biol"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0080","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.bbi.2009.10.002","article-title":"Sustained hippocampal IL-1beta overexpression impairs contextual and spatial memory in transgenic mice","volume":"24","author":"Hein","year":"2010","journal-title":"Brain Behav Immun"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0085","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1007\/s00702-010-0438-z","article-title":"Neuroinflammatory processes in Alzheimer\u2019s disease","volume":"117","author":"Heneka","year":"2010","journal-title":"J Neural Transm"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0090","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ijdevneu.2005.11.001","article-title":"Neuroinflammation and regeneration in the early stages of Alzheimer\u2019s disease pathology","volume":"24","author":"Hoozemans","year":"2006","journal-title":"Int J Dev Neurosci"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0095","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1016\/j.neuropharm.2010.02.003","article-title":"Microglia signaling as a target of donepezil","volume":"58","author":"Hwang","year":"2010","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0100","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3233\/JAD-122077","article-title":"Involvement of insulin-degrading enzyme in insulin- and atrial natriuretic peptide-sensitive internalization of amyloid-beta peptide in mouse brain capillary endothelial cells","volume":"38","author":"Ito","year":"2014","journal-title":"J Alzheimers Dis"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0105","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1742-2094-2-23","article-title":"Early correlation of microglial activation with enhanced tumor necrosis factor-alpha and monocyte chemoattractant protein-1 expression specifically within the entorhinal cortex of triple transgenic Alzheimer\u2019s disease mice","volume":"2","author":"Janelsins","year":"2005","journal-title":"J Neuroinflammation"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0110","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.2353\/ajpath.2008.080528","article-title":"Chronic neuron-specific tumor necrosis factor-alpha expression enhances the local inflammatory environment ultimately leading to neuronal death in 3xTg-AD mice","volume":"173","author":"Janelsins","year":"2008","journal-title":"Am J Pathol"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0115","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S1389-0344(01)00067-3","article-title":"Co-expression of multiple transgenes in mouse CNS: a comparison of strategies","volume":"17","author":"Jankowsky","year":"2001","journal-title":"Biomol Eng"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0120","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.neuro.2013.10.004","article-title":"Donepezil inhibits the amyloid-beta oligomer-induced microglial activation in vitro and in vivo","volume":"40","author":"Kim","year":"2014","journal-title":"Neurotoxicology"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0125","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1038\/npp.2013.70","article-title":"Blockade of Tau hyperphosphorylation and Abeta(1)(-)(4)(2) generation by the aminotetrahydrofuran derivative ANAVEX2-73, a mixed muscarinic and sigma(1) receptor agonist, in a nontransgenic mouse model of Alzheimer\u2019s disease","volume":"38","author":"Lahmy","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0130","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1097\/01.jnen.0000235853.70092.ba","article-title":"Plaque-associated overexpression of insulin-degrading enzyme in the cerebral cortex of aged transgenic tg2576 mice with Alzheimer pathology","volume":"65","author":"Leal","year":"2006","journal-title":"J Neuropathol Exp Neurol"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0135","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/S0896-6273(03)00787-6","article-title":"Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death","volume":"40","author":"Leissring","year":"2003","journal-title":"Neuron"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0140","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.3892\/mmr.2012.1102","article-title":"Expression of APP, BACE1, AChE and ChAT in an AD model in rats and the effect of donepezil hydrochloride treatment","volume":"6","author":"Li","year":"2012","journal-title":"Mol Med Rep"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0145","doi-asserted-by":"crossref","first-page":"5709","DOI":"10.1523\/JNEUROSCI.20-15-05709.2000","article-title":"Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer\u2019s disease","volume":"20","author":"Lim","year":"2000","journal-title":"J Neurosci"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0150","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.2353\/ajpath.2009.090059","article-title":"Interferon-{gamma} differentially affects Alzheimer\u2019s disease pathologies and induces neurogenesis in triple transgenic-AD mice","volume":"175","author":"Mastrangelo","year":"2009","journal-title":"Am J Pathol"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0160","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jneuroim.2009.02.003","article-title":"Characterization of the microglial phenotype under specific pro-inflammatory and anti-inflammatory conditions: effects of oligomeric and fibrillar amyloid-beta","volume":"210","author":"Michelucci","year":"2009","journal-title":"J Neuroimmunol"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0165","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1097\/NEN.0b013e3181afe475","article-title":"Neprilysin and insulin-degrading enzyme levels are increased in Alzheimer disease in relation to disease severity","volume":"68","author":"Miners","year":"2009","journal-title":"J Neuropathol Exp Neurol"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0170","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1016\/j.ajpath.2011.07.001","article-title":"Ablation of TNF-RI\/RII expression in Alzheimer\u2019s disease mice leads to an unexpected enhancement of pathology: implications for chronic pan-TNF-alpha suppressive therapeutic strategies in the brain","volume":"179","author":"Montgomery","year":"2011","journal-title":"Am J Pathol"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0175","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/j.neuroscience.2009.08.073","article-title":"Sustained expression of interleukin-1beta in mouse hippocampus impairs spatial memory","volume":"164","author":"Moore","year":"2009","journal-title":"Neuroscience"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0180","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0165-0270(84)90007-4","article-title":"Developments of a water-maze procedure for studying spatial learning in the rat","volume":"11","author":"Morris","year":"1984","journal-title":"J Neurosci Methods"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0185","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.nlm.2007.10.002","article-title":"On the participation of mTOR in recognition memory","volume":"89","author":"Myskiw","year":"2008","journal-title":"Neurobiol Learn Mem"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0190","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.ejphar.2012.12.023","article-title":"Characterization of cognitive deficits in a transgenic mouse model of Alzheimer\u2019s disease and effects of donepezil and memantine","volume":"703","author":"Nagakura","year":"2013","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0195","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jneuroim.2008.06.018","article-title":"Suppression of neuroinflammation and immunomodulation by the acetylcholinesterase inhibitor rivastigmine","volume":"203","author":"Nizri","year":"2008","journal-title":"J Neuroimmunol"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0200","doi-asserted-by":"crossref","first-page":"5219","DOI":"10.1073\/pnas.0600506103","article-title":"Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia","volume":"103","author":"Pavlov","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0205","doi-asserted-by":"crossref","first-page":"32730","DOI":"10.1074\/jbc.273.49.32730","article-title":"Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation","volume":"273","author":"Qiu","year":"1998","journal-title":"J Biol Chem"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0210","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.cell.2009.01.038","article-title":"A Nurr1\/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death","volume":"137","author":"Saijo","year":"2009","journal-title":"Cell"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0215","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jneuroim.2014.06.008","article-title":"Active immunotherapy facilitates Abeta plaque removal following through microglial activation without obvious T cells infiltrating the CNS","volume":"274","author":"Sha","year":"2014","journal-title":"J Neuroimmunol"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0220","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1172\/JCI31450","article-title":"Sustained hippocampal IL-1 beta overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology","volume":"117","author":"Shaftel","year":"2007","journal-title":"J Clin Invest"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0225","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1046\/j.1471-4159.2004.02347.x","article-title":"Cholinergic modulation of microglial activation by alpha 7 nicotinic receptors","volume":"89","author":"Shytle","year":"2004","journal-title":"J Neurochem"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0230","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.neulet.2008.04.025","article-title":"Increased expression of Abeta degrading enzyme IDE in the cortex of transgenic mice with Alzheimer\u2019s disease-like neuropathology","volume":"438","author":"Vepsalainen","year":"2008","journal-title":"Neurosci Lett"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0235","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/87945","article-title":"TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice","volume":"7","author":"Wyss-Coray","year":"2001","journal-title":"Nat Med"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0240","doi-asserted-by":"crossref","first-page":"609","DOI":"10.3109\/00207454.2013.865027","article-title":"Abeta-induced microglial cell activation is inhibited by baicalin through the JAK2\/STAT3 signaling pathway","volume":"124","author":"Xiong","year":"2014","journal-title":"Int J Neurosci"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0245","doi-asserted-by":"crossref","first-page":"295","DOI":"10.3233\/JAD-2010-100681","article-title":"Anti-inflammatory action of donepezil ameliorates tau pathology, synaptic loss, and neurodegeneration in a tauopathy mouse model","volume":"22","author":"Yoshiyama","year":"2010","journal-title":"J Alzheimers Dis"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0250","doi-asserted-by":"crossref","first-page":"801","DOI":"10.3233\/JAD-2012-120151","article-title":"Novel object recognition as a facile behavior test for evaluating drug effects in AbetaPP\/PS1 Alzheimer\u2019s disease mouse model","volume":"31","author":"Zhang","year":"2012","journal-title":"J Alzheimers Dis"},{"key":"10.1016\/j.neuroscience.2015.01.058_b0255","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1016\/j.freeradbiomed.2012.01.023","article-title":"Early memory deficits precede plaque deposition in APPswe\/PS1dE9 mice: involvement of oxidative stress and cholinergic dysfunction","volume":"52","author":"Zhang","year":"2012","journal-title":"Free Radic Biol Med"}],"container-title":["Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0306452215001165?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0306452215001165?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T22:48:37Z","timestamp":1589496517000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0306452215001165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4]]},"references-count":50,"alternative-id":["S0306452215001165"],"URL":"https:\/\/doi.org\/10.1016\/j.neuroscience.2015.01.058","relation":{},"ISSN":["0306-4522"],"issn-type":[{"value":"0306-4522","type":"print"}],"subject":[],"published":{"date-parts":[[2015,4]]}}}