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We have shown that experimental LC lesions in the Tg344-19 AD rat model result in parenchymal arteriole (PA) stenosis, blood-brain barrier permeability, amyloid angiopathy, and cognitive impairment. Here, we show that PAs from LC-lesioned Tg344-19 AD rats displayed increased myogenic tone and decreased responsiveness to TRPV4 channel agonists, which was reversible by NE replacement. MRI studies indicated reduced forebrain perfusion and fractional anisotropy in LC-lesioned animals compared to controls. Targeting LC-mediated effects on cerebral hemodynamics presents a compelling AD therapeutic target.<\/jats:p>","DOI":"10.1177\/13872877261496548","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:51:47Z","timestamp":1792147907000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Locus coeruleus degeneration impairs forebrain arteriole physiology and perfusion in a rat model of Alzheimer's disease"],"prefix":"10.1177","author":[{"given":"Mahsa","family":"Gifani","sequence":"first","affiliation":[{"name":"Michigan State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura C.","family":"Chambers","sequence":"additional","affiliation":[{"name":"Michigan State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6874-2252","authenticated-orcid":false,"given":"Zachary","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Michigan State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4063-4422","authenticated-orcid":false,"given":"John S.","family":"Beck","sequence":"additional","affiliation":[{"name":"Michigan State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Wiseman","sequence":"additional","affiliation":[{"name":"Michigan State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunqi","family":"Qian","sequence":"additional","affiliation":[{"name":"Michigan State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M.","family":"Dorrance","sequence":"additional","affiliation":[{"name":"Michigan State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2851-9763","authenticated-orcid":false,"given":"Scott E.","family":"Counts","sequence":"additional","affiliation":[{"name":"Michigan State University"},{"name":"Michigan State University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.10.007"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2016.05.030"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2007.01.045"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30029-1"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-014-0206-2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1179\/016164104225016272"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21706"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2011.01221.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0718-6"},{"key":"e_1_3_3_12_2","first-page":"823525","article-title":"Regulation of cerebral blood flow","volume":"2011","author":"Peterson EC","year":"2011","unstructured":"Peterson EC, Wang Z, Britz G. 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