{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:12:05Z","timestamp":1790277125936,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG000213"],"award-info":[{"award-number":["AG000213"]}],"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":["AG040178"],"award-info":[{"award-number":["AG040178"]}],"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":["AG057408"],"award-info":[{"award-number":["AG057408"]}],"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":["P30\u2010AG062715"],"award-info":[{"award-number":["P30\u2010AG062715"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["P51OD011106"],"award-info":[{"award-number":["P51OD011106"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001642","name":"Glenn Foundation for Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001642","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000965","name":"American Federation for Aging Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000965","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Age is a major risk factor for late\u2010onset Alzheimer's disease (AD) but seldom features in laboratory models of the disease. Furthermore, heterogeneity in size and density of AD plaques observed in individuals are not recapitulated in transgenic mouse models, presenting an incomplete picture. We show that the amyloid plaque microenvironment is not equivalent between rodent and primate species, and that differences in the impact of AD pathology on local metabolism and inflammation might explain established differences in neurodegeneration and functional decline. Using brain tissue from transgenic APP\/PSEN1 mice, rhesus monkeys with age\u2010related amyloid plaques, and human subjects with confirmed AD, we report altered energetics in the plaque microenvironment. Metabolic features included changes in mitochondrial distribution and enzymatic activity, and changes in redox cofactors NAD(P)H that were shared among species. A greater burden of lipofuscin was detected in the brains from monkeys and humans of advanced age compared to transgenic mice. Local inflammatory signatures indexed by astrogliosis and microglial activation were detected in each species; however, the inflamed zone was considerably larger for monkeys and humans. These data demonstrate the advantage of nonhuman primates in modeling the plaque microenvironment, and provide a new framework to investigate how AD pathology might contribute to functional loss.<\/jats:p>","DOI":"10.1111\/acel.13374","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T13:22:22Z","timestamp":1620307342000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Rhesus monkeys as a translational model for late\u2010onset Alzheimer's disease"],"prefix":"10.1111","volume":"20","author":[{"given":"Dylan C.","family":"Souder","sequence":"first","affiliation":[{"name":"Division of Geriatrics Department of Medicine SMPH Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle A.","family":"Dreischmeier","sequence":"additional","affiliation":[{"name":"Division of Geriatrics Department of Medicine SMPH Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex B.","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Geriatrics Department of Medicine SMPH Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Wright","sequence":"additional","affiliation":[{"name":"Division of Geriatrics Department of Medicine SMPH Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Martin","sequence":"additional","affiliation":[{"name":"Biology of Aging Laboratory Center for American Indian and Rural Health Equity Montana State University Bozeman MT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Abdul Kader","family":"Sagar","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Wisconsin Madison Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin W.","family":"Eliceiri","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Wisconsin Madison Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahriar M.","family":"Salamat","sequence":"additional","affiliation":[{"name":"Department of Pathology Laboratory Medicine University of Wisconsin Madison Madison WI USA"},{"name":"Neurological Surgery University of Wisconsin Madison Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara B.","family":"Bendlin","sequence":"additional","affiliation":[{"name":"Division of Geriatrics Department of Medicine SMPH Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricki J.","family":"Colman","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center University of Wisconsin Madison Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Mark","family":"Beasley","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Alabama Birmingham AL USA"},{"name":"GRECC Birmingham\/Atlanta Veterans Administration Hospital Birmingham AL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0864-7998","authenticated-orcid":false,"given":"Rozalyn M.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Division of Geriatrics Department of Medicine SMPH Madison WI USA"},{"name":"GRECC William S. Middleton Memorial Veterans Hospital Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12192"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4943(01)00223-0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2010.04.008"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2012.162"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-018-0057-5"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1173635"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4557"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-051116-052358"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7176"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.12.056"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1662-x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/bss0670195"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0312-8"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0798-827"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000329544"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1354.065"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.10.007"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30077-7"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.05.006"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2553-12.2012"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-420138-5.00028-8"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2010.07.006"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2117-15.2016"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12418"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.04.045"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14063"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2015.6593"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2009.10.006"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00464"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30403-4"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.11.005"},{"issue":"6","key":"e_1_2_9_33_1","first-page":"1183","article-title":"Apolipoprotein E4 and beta amyloid in senile plaques and cerebral blood vessels of aged rhesus monkeys","volume":"144","author":"Poduri A.","year":"1994","journal-title":"American Journal of Pathology"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.1991.tb00672.x"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12091"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.31887\/DCNS.2009.11.2\/cqiu"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(00)00166-2"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.01.007"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2013.02.046"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2012.00031"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23782"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.09.010"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00476-7"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-017-1383-5"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000306313.89165.ef"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.2337\/db11-1187"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13374","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.13374","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13374","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T21:31:56Z","timestamp":1693344716000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.13374"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,5]]},"references-count":45,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1111\/acel.13374"],"URL":"https:\/\/doi.org\/10.1111\/acel.13374","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,5]]},"assertion":[{"value":"2020-12-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13374"}}