{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:22:15Z","timestamp":1783012935315,"version":"3.54.6"},"reference-count":69,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100008386","name":"Marmara \u00dcniversitesi","doi-asserted-by":"publisher","award":["SAG\u2010A\u2010110618\u20100292"],"award-info":[{"award-number":["SAG\u2010A\u2010110618\u20100292"]}],"id":[{"id":"10.13039\/501100008386","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Type 2 diabetes mellitus (T2DM) contributes notably to the development and progression of Alzheimer's disease (\n                    <jats:sc>AD<\/jats:sc>\n                    ) through overlapping pathological mechanisms such as insulin resistance, amyloid\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    ) accumulation and tau hyperphosphorylation. Sodium\u2013glucose cotransporter\u20102 (SGLT2) inhibitors have recently emerged as promising candidates for neuroprotection in metabolic disorders. The present work explored the potential therapeutic impact of the SGLT2 inhibitor empagliflozin (EMPA) compared with the acetylcholinesterase inhibitor rivastigmine (RIV) in a T2DM\u2010induced\n                    <jats:sc>AD<\/jats:sc>\n                    rat model. The T2DM\u2010\n                    <jats:sc>AD<\/jats:sc>\n                    model was established using a high\u2010fat diet in combination with subsequent low\u2010dose streptozotocin (35\u2009mg\/kg) administration. Metabolic, behavioural, biochemical, molecular and histopathological parameters were assessed to evaluate disease progression and treatment efficacy. EMPA significantly improved glucose metabolism, lowered nonfasting blood glucose, enhanced oral glucose tolerance and restored insulin levels in peripheral and central tissues. EMPA ameliorated short\u2010term and spatial memory deficits and reduced A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    and phosphorylated tau levels in the brain, serum and pancreas and normalized acetylcholinesterase and glycogen kinase\u20103\n                    <jats:italic>\u03b2<\/jats:italic>\n                    expression. Histological and immunohistochemical analyses corroborated these neuroprotective effects, revealing reduced neurodegeneration and proteinopathy in the cerebral cortex and hippocampus. EMPA exerts multifaceted neuroprotective and metabolic benefits in a T2DM\u2010induced\n                    <jats:sc>AD<\/jats:sc>\n                    model, offering a therapeutic advantage over RIV by targeting both peripheral metabolic dysfunction and central neurodegeneration. By demonstrating that modulation of systemic glucose homeostasis can directly influence amyloid and tau pathology as well as cognitive outcomes, these findings provide important insight into the metabolic\u2013neurodegenerative interface and highlight SGLT2 inhibition as a promising strategy for diabetes\u2010associated cognitive decline and\n                    <jats:sc>AD<\/jats:sc>\n                    within the field of neuroscience.\n                  <\/jats:p>","DOI":"10.1111\/ejn.70495","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T03:14:04Z","timestamp":1776309244000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of Amyloid and Tau Pathology by Empagliflozin in a High\u2010Fat Diet and Streptozotocin\u2010Induced Type 2 Diabetes\u2010Associated Alzheimer's Model"],"prefix":"10.1111","volume":"63","author":[{"given":"Ayse\u00a0Nur","family":"Hazar\u2010Yavuz","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Marmara University  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Busra","family":"Ertas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Marmara University  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rumeysa\u00a0Keles","family":"Kaya","sequence":"additional","affiliation":[{"name":"Department of International Medical Pharmacology, Faculty of Medicine Health Sciences University  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadime","family":"Topal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Marmara University  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcl\u00a0Sinemcan","family":"Kabata\u015f","sequence":"additional","affiliation":[{"name":"Stem Cell and Gene Therapies Research and Applied Center, Faculty of Medicine Kocaeli University  \u0130zmit T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candan","family":"Altunta\u015f","sequence":"additional","affiliation":[{"name":"Stem Cell and Gene Therapies Research and Applied Center, Faculty of Medicine Kocaeli University  \u0130zmit T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levent","family":"Kabasakal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Marmara University  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusufhan","family":"Yazir","sequence":"additional","affiliation":[{"name":"Stem Cell and Gene Therapies Research and Applied Center, Faculty of Medicine Kocaeli University  \u0130zmit T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5398-6801","authenticated-orcid":false,"given":"Muhammet\u00a0Emin","family":"Cam","sequence":"additional","affiliation":[{"name":"MecNano Technologies Cube Incubation, Teknopark Istanbul  Istanbul T\u00fcrkiye"},{"name":"Department of Pharmacology, Faculty of Pharmacy Istanbul Kent University  Istanbul T\u00fcrkiye"},{"name":"ResearchKent, Istanbul Kent University  Istanbul T\u00fcrkiye"},{"name":"Biomedical Engineering Department University of Aveiro  Aveiro Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2011.03.011"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2020.104707"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010\u2010022\u201004549\u20103"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.2\u2010151.v1"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2017.08.013"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.03.011"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.56042\/ijeb.v62i12.3594"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14207"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2018.10.028"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12020382"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.4103\/2230\u20108210.183480"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14017"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201093483\u20107"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263\u2010019\u201000613\u20107"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/6143081"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031\u2010007\u20109002\u20101"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2022.01.017"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116541"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u20102010\u20101404"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.9734\/ajrb\/2021\/v8i230176"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176275"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.9b00286"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2023.122716"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1631\/jzus.B1700254"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20200754"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nsa.2024.105068"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.29228\/jrp.128"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beproc.2011.12.004"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010020\u201000607\u20104"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.01.040"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010017\u20100825\u20107"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12603\u2010011\u20100095\u20104"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0160\u20105402(86)90027\u20106"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2021.105158"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17040503"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2025.109063"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933\u2010014\u20100148\u20101"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u201012\u2010804766\u20108.00009\u20101"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.3791\/55718"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010160266"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010160761"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210\u2010015\u20101134\u20101"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2008.08.019"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE\u201017\u20100263"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.01.013"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165\u20100270(84)90007\u20104"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2023.12.013"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0149\u20102918(98)80127\u20106"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010023\u201003408\u20106"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0002\u20109440(10)63774\u20101"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.2174\/18715273113126660160"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2017.08.005"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2019.03.007"},{"issue":"4","key":"e_1_2_11_56_1","first-page":"362","article-title":"The Effect of Hydroalcoholic Extract of Ziziphora clinopodioides L. on Spatial Memory and Neuronal Density of Hippocampal CA1 Region in Rats With Sporadic Alzheimer's Disease","volume":"9","author":"Sedighi S.","year":"2019","journal-title":"Avicenna Journal of Phytomedicine"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/bab.1319"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26036"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010019\u201001858\u20105"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867325666181009122452"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2005.05.004"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2040\u20101124.2011.00170.x"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.4103\/abr.abr_8_17"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018010103"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph13110379"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.02.011"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.17055"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00296.2010"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00317.2012"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100404.2007.00928.x"}],"container-title":["European Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejn.70495","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ejn.70495","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejn.70495","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T16:50:37Z","timestamp":1783011037000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejn.70495"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":69,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/ejn.70495"],"URL":"https:\/\/doi.org\/10.1111\/ejn.70495","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/EJN.70495\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.70495\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.70495\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.70495\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.70495\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.70495\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.70495\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.70495\/v1\/review1","asserted-by":"object"}]},"ISSN":["0953-816X","1460-9568"],"issn-type":[{"value":"0953-816X","type":"print"},{"value":"1460-9568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-08-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70495"}}