{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:30:21Z","timestamp":1787610621119,"version":"build-2736575974"},"posted":{"date-parts":[[2026,6,3]]},"group-title":"Neuroscience","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P20 GM130447"],"award-info":[{"award-number":["P20 GM130447"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32 AG076407"],"award-info":[{"award-number":["T32 AG076407"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008539","name":"CurePSP","doi-asserted-by":"crossref","award":["703-2024-07"],"award-info":[{"award-number":["703-2024-07"]}],"id":[{"id":"10.13039\/100008539","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Sleep disruption is an early and pervasive feature of Alzheimer\u2019s disease (AD), yet the circuit mechanisms linking tau pathology to sleep-wake dysfunction remain unresolved. Here, we identify melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) as a critical node disrupted in tauopathy. Longitudinal EEG\/EMG recordings in\n                  <jats:italic>PS19<\/jats:italic>\n                  mice reveal progressive impairments in sleep architecture and homeostasis. Histological analyses revealed significant degeneration of both MCH neurons and the neighboring hypocretin (Hcrt) neuronal population in the LH at late stages of tauopathy.\n                  <jats:italic>In vivo<\/jats:italic>\n                  fiber photometry recordings demonstrated a selective functional impairment of MCH neurons, characterized by reduced activity during REM sleep, whereas Hcrt neuronal activity remained largely preserved. In addition, cell-autonomous expression of mutant tau in MCH neurons recapitulates sleep disruption, establishing a causal role. Despite tauopathy-induced neuronal loss and reduced endogenous activity, optogenetic and chemogenetic activation show that MCH neurons retain functional capacity, and their activation restores sleep in aged\n                  <jats:italic>PS19<\/jats:italic>\n                  mice. Together, these findings define a circuit mechanism linking tau pathology to sleep and identify MCH neurons as a tractable therapeutic target.\n                <\/jats:p>","DOI":"10.64898\/2026.05.31.729026","type":"posted-content","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T20:05:14Z","timestamp":1780517114000},"source":"Crossref","is-referenced-by-count":1,"title":["Hypothalamic MCH neurons links tau pathology to sleep disruption"],"prefix":"10.64898","author":[{"given":"Ke","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE 68106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyin","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE 68106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruilin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE 68106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE 68106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wyatt D.","family":"Morse","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE 68106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leann","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE 68106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoling","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE 68106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dequan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE 68106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE 68106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026060611350634000_2026.05.31.729026v1.1","doi-asserted-by":"crossref","unstructured":"B. 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