{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:05:13Z","timestamp":1787583913931,"version":"build-2736575974"},"reference-count":64,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R01AA026082"],"award-info":[{"award-number":["R01AA026082"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["IK6BX004214"],"award-info":[{"award-number":["IK6BX004214"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcohol, Clinical and Experimental Research"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by the buildup of amyloid\u2010\u03b2 and tau protein tangles. Alcohol use has been identified as a risk factor for AD; however, the molecular mechanisms underlying this potential causal link remain elusive. An emerging area of research focuses on the role of microglia, the brain's innate immune cells, in AD pathogenesis, with evidence suggesting that alcohol exposure may prime microglia to exhibit an exaggerated immune response when they are subsequently exposed to proinflammatory stimuli.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used a single 10\u2010day chronic\u2010plus\u2010binge alcohol exposure model in male and female C57BL\/6J mice aged 8\u201310\u2009weeks One month later, tauopathy was induced via adenoviral vector (AAV)\u2010mediated overexpression of h\u2010p301L Tau. After 2.5\u2009months, the mice underwent behavioral and cognitive testing. Two weeks later, microglia were collected using fluorescence\u2010activated cell sorting (FACS) and processed for unbiased, mass spectrometry\u2010based proteomic analysis to determine the molecular pathways related to microglial reactivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Microglia from mice exposed to alcohol in young adulthood exhibited a blunted immune response when challenged with\n                      <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>\n                      \u2010mediated delivery and accumulation of human tau later in life. This was characterized by decreased expression of\n                      <jats:styled-content style=\"fixed-case\">MHC II<\/jats:styled-content>\n                      \u2010 and interferon\u2010associated proteins and bioinformatic prediction of inhibited inflammation\u2010related pathways in the absence of gross histological, behavioral, or cognitive deficits. These results demonstrate unique, temporally specific microglial reactivity to tau that is modulated by early adulthood alcohol exposure, implicating a microglial response that could negatively affect the mechanisms necessary for tau clearance and potentially exacerbate tau pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides novel insights into the long\u2010term effects of alcohol exposure in early adulthood on microglial function and the complexity of context\u2010dependent microglial involvement in tauopathy. Consideration of early\u2010adulthood environmental factors is critical for understanding and potentially mitigating the risk of neurodegenerative diseases, such as AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.70034","type":"journal-article","created":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T05:59:08Z","timestamp":1742709548000},"page":"985-1000","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Chronic alcohol exposure during young adulthood attenuates microglial reactivity and downstream immune response pathways in a mouse model of tauopathy later in life"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4274-9843","authenticated-orcid":false,"given":"Tiara","family":"Wolf","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Moss","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Brain Repair University of South Florida Morsani College of Medicine  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Hudson","sequence":"additional","affiliation":[{"name":"James A. Haley Veterans Hospital Research Service  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis M.","family":"Winters","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma S.","family":"Abdelmaboud","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Brain Repair University of South Florida Morsani College of Medicine  Tampa Florida USA"},{"name":"James A. Haley Veterans Hospital Research Service  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Avlas","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Brain Repair University of South Florida Morsani College of Medicine  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7785-3051","authenticated-orcid":false,"given":"Jessica","family":"Wohlfahrt","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Guergues","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9657-7725","authenticated-orcid":false,"given":"Paula C.","family":"Bickford","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Brain Repair University of South Florida Morsani College of Medicine  Tampa Florida USA"},{"name":"James A. Haley Veterans Hospital Research Service  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1399-0256","authenticated-orcid":false,"suffix":"Jr.","given":"Stanley M.","family":"Stevens","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI79590"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2019.09.086"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.3.631"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4132"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2016.10.010"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.884170"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M115.053926"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.032"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.08.023"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.049012"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/10738584211024531"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv336"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0638-x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2013552117"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(89)90329-8"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2020.103753"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.08.001"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231810224"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2011-101866"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2017.11.002"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3554"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.irn.2019.10.017"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170490"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12816"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2200746"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0560-7"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2834"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2019.52.2.129"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-00435-y"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-8329(03)00025-9"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab337"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0920-8"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv081"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.12.016"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.09.039"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2011.01.006"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104520"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.14694"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25031603"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/neuroglia5030020"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2022.101580"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3271-9_21"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2012.12.011"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2014.175"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.10.020"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00433809"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1038"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.38"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2015.11.011"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.14420"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-199935"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2023.578031"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01911-4"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-1680-z"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.03.005"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2022.886634"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3901"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-130110"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.05.048"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29552-6"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-018-0296-y"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.01.010"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02463-5"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2021.15"}],"container-title":["Alcohol, Clinical and Experimental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.70034","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acer.70034","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.70034","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:12:04Z","timestamp":1780474324000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acer.70034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,21]]},"references-count":64,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1111\/acer.70034"],"URL":"https:\/\/doi.org\/10.1111\/acer.70034","archive":["Portico"],"relation":{},"ISSN":["2993-7175","2993-7175"],"issn-type":[{"value":"2993-7175","type":"print"},{"value":"2993-7175","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,21]]},"assertion":[{"value":"2024-09-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}