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Emerging evidence suggests that AO exposures cause toxic and degenerative pathologies that may increase the risk for Alzheimer\u2019s disease (AD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>This study investigates the effects of the two main AO constituents on key molecular and biochemical indices of AD-type neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Long Evans rat frontal lobe slice cultures treated with 250\u03bcg\/ml of 2,4-D, 2,4,5-T, or both ( D\u200a+\u200aT) were evaluated for cytotoxicity, oxidative injury, mitochondrial function, and AD biomarker expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Treatment with the AO constituents caused histopathological changes corresponding to neuronal, white matter, and endothelial cell degeneration, and molecular\/biochemical abnormalities indicative of cytotoxic injury, lipid peroxidation, DNA damage, and increased immunoreactivity to activated Caspase 3, glial fibrillary acidic protein, ubiquitin, tau, paired-helical filament phosphorylated tau, A\u03b2PP, A\u03b2, and choline acetyltransferase. Nearly all indices of cellular injury and degeneration were more pronounced in the D\u200a+\u200aT compared with 2,4-D or 2,4,5-T treated cultures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Exposures to AO herbicidal chemicals damage frontal lobe brain tissue with molecular and biochemical abnormalities that mimic pathologies associated with early-stage AD-type neurodegeneration. Additional research is needed to evaluate the long-term effects of AO exposures in relation to aging and progressive neurodegeneration in Vietnam War Veterans.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-230881","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T10:49:33Z","timestamp":1706870973000},"page":"1703-1726","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Agent Orange Herbicidal Toxin-Initiation of Alzheimer-Type Neurodegeneration"],"prefix":"10.1177","volume":"97","author":[{"given":"Suzanne M.","family":"de la Monte","sequence":"first","affiliation":[{"name":"Departments of Pathology and Laboratory Medicine, Neurology, and Neurosurgery, Rhode Island Hospital, Lifespan Academic Institutions, and the Warren Alpert Medical School of Brown University, Providence, RI, USA"},{"name":"Department of Medicine, Rhode Island Hospital, Lifespan Academic Institutions, and the Warren Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rhode Island Hospital, Lifespan Academic Institutions, and the Warren Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,2,2]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-016-0674-0"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1233-3"},{"key":"ref003","first-page":"1357","volume":"118","author":"Li X","year":"2005","journal-title":"Chin Med J (Engl)"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-011-0660-8"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2020.08.003"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.932386"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2021.09.004"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2012.04.001"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2012.00192"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2020.117185"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2009-1070"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2012.07.062"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.3109\/15563658208990397"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-4-54"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2009-1098"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.1002\/ajim.4700180605"},{"key":"ref017","unstructured":"Institute of Medicine (US) Committee to review the health effects in Vietnam veterans of exposure to herbicides (Third Biennial Update) (2001) Veterans and Agent Orange: Update 2000, National Academies Press (US), Washington (DC)."},{"key":"ref018","first-page":"265","volume":"35","author":"Ambrus JL","year":"2004","journal-title":"J Med"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2014.04.027"},{"key":"ref020","unstructured":"Institute of Medicine (1994) Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam, The National Academies Press, Washington (DC)."},{"key":"ref021","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-8080(01)90102-8"},{"key":"ref022","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyl038"},{"key":"ref023","doi-asserted-by":"publisher","DOI":"10.1016\/S0013-9351(88)80039-2"},{"key":"ref024","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1990.03450140046032"},{"key":"ref025","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-199705000-00005"},{"key":"ref026","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a009699"},{"key":"ref027","first-page":"17","volume":"30","author":"de la Monte SM","year":"2022","journal-title":"J Mil Veterans Health"},{"key":"ref028","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.5011"},{"key":"ref029","doi-asserted-by":"publisher","DOI":"10.2486\/indhealth.41.149"},{"key":"ref030","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-813X(01)00052-3"},{"key":"ref031","doi-asserted-by":"publisher","DOI":"10.3961\/jpmph.2013.46.5.213"},{"key":"ref032","unstructured":"GervaisJ, LuukinenB, BuhlK, StoneD (2008) 2,4-D Technical Fact Sheet. 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