{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:05:08Z","timestamp":1790687108263,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,25]]},"group-title":"Physiology","reference-count":72,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01GM128008"],"award-info":[{"award-number":["R01GM128008"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"award":["3R01GM128008-03S1"],"award-info":[{"award-number":["3R01GM128008-03S1"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01GM121102"],"award-info":[{"award-number":["R01GM121102"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1R35GM118182"],"award-info":[{"award-number":["1R35GM118182"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Cholinergic neurons in the dorsal motor nucleus of the vagus (DMN) in the brainstem are a key source of efferent vagus nerve fibers that regulate vital functions, including heart rate and inflammation. Whether the integrity of DMN cholinergic neurons is affected during Alzheimer\u2019s disease (AD) remains unknown. Here, in female and male mice with experimental AD (5xFAD), which exhibit age-dependent memory impairment, basal forebrain cholinergic neurodegeneration, and microglial alterations, we observe a reduction in cholinergic neuron density in the DMN at 6 and 10 months of age. Furthermore, while an important physiological function of DMN cholinergic signaling, such as suppression of heart rate, is preserved in control mice upon electrical DMN stimulation, the extent of suppression diminishes with age in both female and male 5xFAD mice. In addition, while electrical DMN stimulation lowers pro-inflammatory cytokine levels in control mice subjected to endotoxemia, this anti-inflammatory effect is diminished with age in 5xFAD mice, with females showing earlier dysfunction at 6 months. These results reveal previously unrecognized age-dependent cholinergic deficits in the DMN and disrupted brain\u2013to\u2013periphery vagus nerve circuits in experimental AD. These findings advance our understanding of AD mechanisms and are of interest for the development of conceptually novel therapies.<\/jats:p>","DOI":"10.64898\/2026.09.19.752906","type":"posted-content","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T20:25:12Z","timestamp":1790367912000},"source":"Crossref","is-referenced-by-count":0,"title":["Cholinergic impairment in the dorsal motor nucleus of the vagus during experimental Alzheimer\u2019s disease"],"prefix":"10.64898","author":[{"given":"Aidan","family":"Falvey","sequence":"first","affiliation":[{"name":"The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santhoshi P.","family":"Palandira","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA"},{"name":"Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saher","family":"Chaudhry","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua J.","family":"Strohl","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricio T.","family":"Huerta","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA"},{"name":"Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, USA"},{"name":"Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Hempstead, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tea","family":"Tsaava","sequence":"additional","affiliation":[{"name":"The 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Manhasset, NY, USA"},{"name":"Northwell, New Hyde Park, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Koppel","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA"},{"name":"Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, USA"},{"name":"Northwell, New Hyde Park, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef","family":"Al-Abed","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA"},{"name":"Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, USA"},{"name":"Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Hempstead, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Brines","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Marambaud","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA"},{"name":"Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, USA"},{"name":"Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Hempstead, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeeta S.","family":"Chavan","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA"},{"name":"Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, USA"},{"name":"Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Hempstead, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric H.","family":"Chang","sequence":"additional","affiliation":[{"name":"The Feinstein 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