{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:50:01Z","timestamp":1789469401191,"version":"build-2803163510"},"reference-count":78,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,10,28]],"date-time":"2018-10-28T00:00:00Z","timestamp":1540684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG010161"],"award-info":[{"award-number":["P30AG010161"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG019610"],"award-info":[{"award-number":["P30AG019610"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["PO1AG014449"],"award-info":[{"award-number":["PO1AG014449"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["RO1AG042146"],"award-info":[{"award-number":["RO1AG042146"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["RO1AG043375"],"award-info":[{"award-number":["RO1AG043375"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013014","name":"Barrow Neurological Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013014","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Alzheimer's disease (\n                      <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\n                      ) is characterized by degeneration of cholinergic basal forebrain (\n                      <jats:styled-content style=\"fixed-case\">CBF<\/jats:styled-content>\n                      ) neurons in the nucleus basalis of Meynert (nbM), which provides the major cholinergic input to the cortical mantle and is related to cognitive decline in patients with\n                      <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\n                      . Cortical histone deacetylase (\n                      <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>\n                      ) dysregulation has been associated with neuronal degeneration during\n                      <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\n                      progression. However, whether\n                      <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>\n                      alterations play a role in\n                      <jats:styled-content style=\"fixed-case\">CBF<\/jats:styled-content>\n                      degeneration during\n                      <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\n                      onset is unknown. We investigated global HDAC protein levels and nuclear HDAC2 immunoreactivity in tissue containing the nbM, changes and their association with neurofibrillary tangles (NFTs) during the progression of AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used semi\u2010quantitative western blotting and immunohistochemistry to evaluate\n                      <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>\n                      and sirtuin (\n                      <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>\n                      ) levels in individuals that died with a premortem clinical diagnosis of no cognitive impairment (\n                      <jats:styled-content style=\"fixed-case\">NCI<\/jats:styled-content>\n                      ), mild cognitive impairment (\n                      <jats:styled-content style=\"fixed-case\">MCI<\/jats:styled-content>\n                      ), mild\/moderate\n                      <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\n                      (\n                      <jats:styled-content style=\"fixed-case\">mAD<\/jats:styled-content>\n                      ) or severe\n                      <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\n                      (\n                      <jats:styled-content style=\"fixed-case\">sAD<\/jats:styled-content>\n                      ). Quantitative immunohistochemistry was used to identify\n                      <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>\n                      2 protein levels in individual cholinergic nbM nuclei and their colocalization with the early phosphorylated tau marker\n                      <jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content>\n                      8, the late\u2010stage apoptotic tau marker TauC3 and Thioflavin\u2010S, a\u00a0marker of \u03b2\u2010pleated sheet structures in\n                      <jats:styled-content style=\"fixed-case\">NFT<\/jats:styled-content>\n                      s.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In\n                      <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\n                      patients,\n                      <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>\n                      2 protein levels were dysregulated in the basal forebrain region containing cholinergic neurons of the nbM.\n                      <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>\n                      2 nuclear immunoreactivity was reduced in individual cholinergic nbM neurons across disease stages.\n                      <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>\n                      2 nuclear reactivity correlated with multiple cognitive domains and with\n                      <jats:styled-content style=\"fixed-case\">NFT<\/jats:styled-content>\n                      formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings suggest that\n                      <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>\n                      2 dysregulation contributes to cholinergic nbM neuronal dysfunction,\n                      <jats:styled-content style=\"fixed-case\">NFT<\/jats:styled-content>\n                      pathology, and cognitive decline during clinical progression of\n                      <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12518","type":"journal-article","created":{"date-parts":[[2018,9,25]],"date-time":"2018-09-25T14:34:46Z","timestamp":1537886086000},"page":"380-397","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["<scp>HDAC<\/scp>\n                    2 dysregulation in the nucleus basalis of Meynert during the progression of Alzheimer's disease"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6461-9011","authenticated-orcid":false,"given":"L.","family":"Mahady","sequence":"first","affiliation":[{"name":"Department of Neurobiology Barrow Neurological Institute St. Joseph's Hospital and Medical Center Phoenix Arizona USA"},{"name":"Arizona State University Interdisciplinary Graduate Program in Neuroscience Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Nadeem","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Barrow Neurological Institute St. Joseph's Hospital and Medical Center Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Malek\u2010Ahmadi","sequence":"additional","affiliation":[{"name":"Banner Alzheimer's Institute Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Chen","sequence":"additional","affiliation":[{"name":"Banner Alzheimer's Institute Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. E.","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Barrow Neurological Institute St. Joseph's Hospital and Medical Center Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4438-7334","authenticated-orcid":false,"given":"E. J.","family":"Mufson","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Barrow Neurological Institute St. Joseph's Hospital and Medical Center Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(83)90108-2"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410100203"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(86)90142-9"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0317167100037070"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(87)90260-7"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(89)90124-6"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(91)90198-W"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010051068"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(84)90083-6"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318272caab"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.6150.1457"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(82)90045-4"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410320505"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9861(20001106)427:1<19::AID-CNE2>3.0.CO;2-A"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10122"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720507781788774"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567205012666150921100030"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/63.6.641"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410200407"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004019900178"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.07.044"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20100"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2010.01.007"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2011.12.024"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-28383-8_21"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10849"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds125"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07925"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/143269"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05564.x"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0124-15.2016"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05853"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010848"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181922348"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2013.00016"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2008.12.005"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13249"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh589"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3427"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.06.013"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nepig.2014.10.002"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-171032"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2004.09.019"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2003-5201"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2004.08.014"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2016.05.016"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlx120"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000152982.47274.9E"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1999.7086"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.59.2.198"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.10.027"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1037\/0882-7974.17.2.179"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2004.01388.x"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199911000-00004"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(97)00058-4"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70178-3"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20233"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2014.03.012"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchemneu.2011.02.004"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2444-14.2015"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/163140"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2014.08.001"},{"key":"e_1_2_8_65_1","first-page":"220","article-title":"The potential of epigenetic therapies in neurodegenerative diseases","volume":"5","author":"Coppede F","year":"2014","journal-title":"Front Genet"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0097-09.2009"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10069"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.03.003"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01558"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603469200"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-006-0473-0"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2016.5436"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-9-80"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2008.01.010"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-07-02557.2003"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1021\/cn500162j"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2013.05.003"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm500872p"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf7551"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnan.12518","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12518","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nan.12518","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12518","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T07:51:58Z","timestamp":1694332318000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.12518"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,28]]},"references-count":78,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1111\/nan.12518"],"URL":"https:\/\/doi.org\/10.1111\/nan.12518","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,28]]},"assertion":[{"value":"2018-07-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}