{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T06:26:54Z","timestamp":1794119214206,"version":"4.8.0"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["P01NS074969"],"award-info":[{"award-number":["P01NS074969"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["RF1NS090934"],"award-info":[{"award-number":["RF1NS090934"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["RF1AG061776"],"award-info":[{"award-number":["RF1AG061776"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007457","name":"JPB Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007457","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["AARF-21-850865"],"award-info":[{"award-number":["AARF-21-850865"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Neurosci"],"published-print":{"date-parts":[[2025,7]]},"DOI":"10.1038\/s41593-025-01966-7","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T09:04:48Z","timestamp":1748336688000},"page":"1460-1472","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Lemborexant ameliorates tau-mediated sleep loss and neurodegeneration in males in a mouse model of tauopathy"],"prefix":"10.1038","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5807-190X","authenticated-orcid":false,"given":"Samira","family":"Parhizkar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Rensing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Kipnis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihui","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Gent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6362-0141","authenticated-orcid":false,"given":"Eric","family":"Tycksen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7912-2016","authenticated-orcid":false,"given":"Melissa","family":"Manis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choonghee","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier Remolina","family":"Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan E.","family":"Bosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Franke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6362-4767","authenticated-orcid":false,"given":"Carla M.","family":"Yuede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C.","family":"Landsness","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3400-0856","authenticated-orcid":false,"given":"David M.","family":"Holtzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"1966_CR1","doi-asserted-by":"crossref","first-page":"101250","DOI":"10.1016\/j.smrv.2019.101250","volume":"50","author":"OM Bubu","year":"2020","unstructured":"Bubu, O. M. et al. Obstructive sleep apnea, cognition and Alzheimer\u2019s disease: a systematic review integrating three decades of multidisciplinary research. Sleep. Med. Rev. 50, 101250 (2020).","journal-title":"Sleep. Med. Rev."},{"key":"1966_CR2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.smrv.2017.06.010","volume":"40","author":"L Shi","year":"2018","unstructured":"Shi, L. et al. Sleep disturbances increase the risk of dementia: a systematic review and meta-analysis. Sleep. Med. Rev. 40, 4\u201316 (2018).","journal-title":"Sleep. Med. Rev."},{"key":"1966_CR3","doi-asserted-by":"crossref","first-page":"101541","DOI":"10.1016\/j.smrv.2021.101541","volume":"60","author":"CH Lew","year":"2021","unstructured":"Lew, C. H., Petersen, C., Neylan, T. C. & Grinberg, L. T. Tau-driven degeneration of sleep- and wake-regulating neurons in Alzheimer\u2019s disease. Sleep. Med. Rev. 60, 101541 (2021).","journal-title":"Sleep. Med. Rev."},{"key":"1966_CR4","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1093\/jnen\/nlx113","volume":"77","author":"RA Eser","year":"2018","unstructured":"Eser, R. A. et al. Selective vulnerability of brainstem nuclei in distinct tauopathies: a postmortem study. J. Neuropathol. Exp. Neurol. 77, 149\u2013161 (2018).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"1966_CR5","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1016\/j.jalz.2019.06.3916","volume":"15","author":"J Oh","year":"2019","unstructured":"Oh, J. et al. Profound degeneration of wake-promoting neurons in Alzheimer\u2019s disease. Alzheimers Dement. 15, 1253\u20131263 (2019).","journal-title":"Alzheimers Dement."},{"key":"1966_CR6","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.neuron.2025.02.004","volume":"113","author":"S Parhizkar","year":"2025","unstructured":"Parhizkar, S. & Holtzman, D. M. The night\u2019s watch: exploring how sleep protects against neurodegeneration. Neuron 113, 817\u2013837 (2025).","journal-title":"Neuron"},{"key":"1966_CR7","doi-asserted-by":"crossref","first-page":"830","DOI":"10.2967\/jnumed.121.263694","volume":"63","author":"M Malpetti","year":"2022","unstructured":"Malpetti, M., La Joie, R. & Rabinovici, G. D. Tau beats amyloid in predicting brain atrophy in Alzheimer disease: implications for prognosis and clinical trials. J. Nucl. Med. 63, 830\u2013832 (2022).","journal-title":"J. Nucl. Med."},{"key":"1966_CR8","doi-asserted-by":"crossref","first-page":"eaau6550","DOI":"10.1126\/scitranslmed.aau6550","volume":"11","author":"BP Lucey","year":"2019","unstructured":"Lucey, B. P. et al. Reduced non-rapid eye movement sleep is associated with tau pathology in early Alzheimer\u2019s disease. Sci. Transl. Med. 11, eaau6550 (2019).","journal-title":"Sci. Transl. Med."},{"key":"1966_CR9","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/acn3.390","volume":"4","author":"JK Holth","year":"2017","unstructured":"Holth, J. K., Mahan, T. E., Robinson, G. O., Rocha, A. & Holtzman, D. M. Altered sleep and EEG power in the P301S Tau transgenic mouse model. Ann. Clin. Transl. Neurol. 4, 180\u2013190 (2017).","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"1966_CR10","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1126\/science.aav2546","volume":"363","author":"JK Holth","year":"2019","unstructured":"Holth, J. K. et al. The sleep\u2013wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans. Science 363, 880\u2013884 (2019).","journal-title":"Science"},{"key":"1966_CR11","doi-asserted-by":"crossref","first-page":"10255","DOI":"10.1523\/JNEUROSCI.0275-18.2018","volume":"38","author":"Y Zhu","year":"2018","unstructured":"Zhu, Y. et al. Chronic sleep disruption advances the temporal progression of tauopathy in P301S mutant mice. J. Neurosci. 38, 10255\u201310270 (2018).","journal-title":"J. Neurosci."},{"key":"1966_CR12","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1097\/00004714-200212000-00007","volume":"22","author":"JC Verster","year":"2002","unstructured":"Verster, J. C. et al. Residual effects of middle-of-the-night administration of zaleplon and zolpidem on driving ability, memory functions, and psychomotor performance. J. Clin. Psychopharmacol. 22, 576\u2013583 (2002).","journal-title":"J. Clin. Psychopharmacol."},{"key":"1966_CR13","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/j.1365-2869.2009.00757.x","volume":"19","author":"PT Morgan","year":"2010","unstructured":"Morgan, P. T., Kehne, J. H., Sprenger, K. J. & Malison, R. T. Retrograde effects of triazolam and zolpidem on sleep-dependent motor learning in humans. J. Sleep. Res. 19, 157\u2013164 (2010).","journal-title":"J. Sleep. Res."},{"key":"1966_CR14","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.sleep.2020.11.004","volume":"79","author":"R Robbins","year":"2021","unstructured":"Robbins, R. et al. Sleep medication use and incident dementia in a nationally representative sample of older adults in the US. Sleep. Med. 79, 183\u2013189 (2021).","journal-title":"Sleep. Med."},{"key":"1966_CR15","doi-asserted-by":"crossref","first-page":"e0174730","DOI":"10.1371\/journal.pone.0174730","volume":"12","author":"K Donnelly","year":"2017","unstructured":"Donnelly, K., Bracchi, R., Hewitt, J., Routledge, P. A. & Carter, B. Benzodiazepines, Z-drugs and the risk of hip fracture: a systematic review and meta-analysis. PLoS ONE 12, e0174730 (2017).","journal-title":"PLoS ONE"},{"key":"1966_CR16","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0092-8674(00)80949-6","volume":"92","author":"T Sakurai","year":"1998","unstructured":"Sakurai, T. et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92, 573\u2013585 (1998).","journal-title":"Cell"},{"key":"1966_CR17","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1073\/pnas.95.1.322","volume":"95","author":"L de Lecea","year":"1998","unstructured":"de Lecea, L. et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc. Natl Acad. Sci. USA 95, 322\u2013327 (1998).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1966_CR18","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/alz.12035","volume":"16","author":"WJ Herring","year":"2020","unstructured":"Herring, W. J. et al. Polysomnographic assessment of suvorexant in patients with probable Alzheimer\u2019s disease dementia and insomnia: a randomized trial. Alzheimers Dement. 16, 541\u2013551 (2020).","journal-title":"Alzheimers Dement."},{"key":"1966_CR19","doi-asserted-by":"crossref","first-page":"7","DOI":"10.14283\/jpad.2020.69","volume":"8","author":"M Moline","year":"2021","unstructured":"Moline, M. et al. Safety and efficacy of lemborexant in patients with irregular sleep\u2013wake rhythm disorder and Alzheimer\u2019s disease dementia: results from a phase 2 randomized clinical trial. J. Prev. Alzheimers Dis. 8, 7\u201318 (2021).","journal-title":"J. Prev. Alzheimers Dis."},{"key":"1966_CR20","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/ana.26641","volume":"94","author":"BP Lucey","year":"2023","unstructured":"Lucey, B. P. et al. Suvorexant acutely decreases tau phosphorylation and A\u03b2 in the human CNS. Ann. Neurol. 94, 27\u201340 (2023).","journal-title":"Ann. Neurol."},{"key":"1966_CR21","doi-asserted-by":"crossref","first-page":"zsz076","DOI":"10.1093\/sleep\/zsz076","volume":"42","author":"CT Beuckmann","year":"2019","unstructured":"Beuckmann, C. T., Ueno, T., Nakagawa, M., Suzuki, M. & Akasofu, S. Preclinical in vivo characterization of lemborexant (E2006), a novel dual orexin receptor antagonist for sleep\/wake regulation. Sleep 42, zsz076 (2019).","journal-title":"Sleep"},{"key":"1966_CR22","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.5664\/jcsm.6800","volume":"13","author":"P Murphy","year":"2017","unstructured":"Murphy, P. et al. Lemborexant, a dual orexin receptor antagonist (DORA) for the treatment of insomnia disorder: results from a Bayesian, adaptive, randomized, double-blind, placebo-controlled study. J. Clin. Sleep. Med. 13, 1289\u20131299 (2017).","journal-title":"J. Clin. Sleep. Med."},{"key":"1966_CR23","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.sleep.2021.01.048","volume":"80","author":"J Yardley","year":"2021","unstructured":"Yardley, J. et al. Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: results from a phase 3 randomized clinical trial. Sleep. Med. 80, 333\u2013342 (2021).","journal-title":"Sleep. Med."},{"key":"1966_CR24","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1126\/science.1180962","volume":"326","author":"JE Kang","year":"2009","unstructured":"Kang, J. E. et al. Amyloid-\u03b2 dynamics are regulated by orexin and the sleep\u2013wake cycle. Science 326, 1005\u20131007 (2009).","journal-title":"Science"},{"key":"1966_CR25","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1084\/jem.20141788","volume":"211","author":"JH Roh","year":"2014","unstructured":"Roh, J. H. et al. Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer\u2019s disease. J. Exp. Med. 211, 2487\u20132496 (2014).","journal-title":"J. Exp. Med."},{"key":"1966_CR26","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1002\/ana.21223","volume":"63","author":"KA Josephs","year":"2008","unstructured":"Josephs, K. A. et al. \u03b2-Amyloid burden is not associated with rates of brain atrophy. Ann. Neurol. 63, 204\u2013212 (2008).","journal-title":"Ann. Neurol."},{"key":"1966_CR27","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nature24016","volume":"549","author":"Y Shi","year":"2017","unstructured":"Shi, Y. et al. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature 549, 523\u2013527 (2017).","journal-title":"Nature"},{"key":"1966_CR28","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.neuron.2007.01.010","volume":"53","author":"Y Yoshiyama","year":"2007","unstructured":"Yoshiyama, Y. et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53, 337\u2013351 (2007).","journal-title":"Neuron"},{"key":"1966_CR29","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1084\/jem.20190980","volume":"216","author":"Y Shi","year":"2019","unstructured":"Shi, Y. et al. Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model. J. Exp. Med. 216, 2546\u20132561 (2019).","journal-title":"J. Exp. Med."},{"key":"1966_CR30","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1093\/brain\/awz241","volume":"142","author":"R Mancuso","year":"2019","unstructured":"Mancuso, R. et al. CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice. Brain 142, 3243\u20133264 (2019).","journal-title":"Brain"},{"key":"1966_CR31","doi-asserted-by":"crossref","first-page":"3403","DOI":"10.1111\/bph.15813","volume":"179","author":"RJ Keenan","year":"2022","unstructured":"Keenan, R. J. et al. Differential sleep\/wake response and sex differences following acute suvorexant, MK-1064 and zolpidem administration in the rTg4510 mouse model of tauopathy. Br. J. Pharmacol. 179, 3403\u20133417 (2022).","journal-title":"Br. J. Pharmacol."},{"key":"1966_CR32","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/s41586-023-05788-0","volume":"615","author":"X Chen","year":"2023","unstructured":"Chen, X. et al. Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy. Nature 615, 668\u2013677 (2023).","journal-title":"Nature"},{"key":"1966_CR33","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.immuni.2017.08.008","volume":"47","author":"S Krasemann","year":"2017","unstructured":"Krasemann, S. et al. The TREM2\u2013APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566\u2013581 (2017).","journal-title":"Immunity"},{"key":"1966_CR34","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","volume":"169","author":"H Keren-Shaul","year":"2017","unstructured":"Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer\u2019s disease. Cell 169, 1276\u20131290 (2017).","journal-title":"Cell"},{"key":"1966_CR35","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1084\/jem.20131685","volume":"211","author":"K Yamada","year":"2014","unstructured":"Yamada, K. et al. Neuronal activity regulates extracellular tau in vivo. J. Exp. Med. 211, 387\u2013393 (2014).","journal-title":"J. Exp. Med."},{"key":"1966_CR36","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1038\/nn.4328","volume":"19","author":"JW Wu","year":"2016","unstructured":"Wu, J. W. et al. Neuronal activity enhances tau propagation and tau pathology in vivo. Nat. Neurosci. 19, 1085\u20131092 (2016).","journal-title":"Nat. Neurosci."},{"key":"1966_CR37","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s00401-014-1254-6","volume":"127","author":"Z Ahmed","year":"2014","unstructured":"Ahmed, Z. et al. A novel in vivo model of tau propagation with rapid and progressive neurofibrillary tangle pathology: the pattern of spread is determined by connectivity, not proximity. Acta Neuropathol. 127, 667\u2013683 (2014).","journal-title":"Acta Neuropathol."},{"key":"1966_CR38","doi-asserted-by":"crossref","first-page":"7486","DOI":"10.1523\/JNEUROSCI.19-17-07486.1999","volume":"19","author":"GA Jicha","year":"1999","unstructured":"Jicha, G. A. et al. cAMP-dependent protein kinase phosphorylations on tau in Alzheimer\u2019s disease. J. Neurosci. 19, 7486\u20137494 (1999).","journal-title":"J. Neurosci."},{"key":"1966_CR39","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1124\/jpet.117.241422","volume":"362","author":"CT Beuckmann","year":"2017","unstructured":"Beuckmann, C. T. et al. In vitro and in silico characterization of lemborexant (E2006), a novel dual orexin receptor antagonist. J. Pharmacol. Exp. Ther. 362, 287\u2013295 (2017).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"1966_CR40","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1084\/jem.20160833","volume":"213","author":"JL Guo","year":"2016","unstructured":"Guo, J. L. et al. Unique pathological tau conformers from Alzheimer\u2019s brains transmit tau pathology in nontransgenic mice. J. Exp. Med. 213, 2635\u20132654 (2016).","journal-title":"J. Exp. Med."},{"key":"1966_CR41","doi-asserted-by":"crossref","first-page":"zsx154","DOI":"10.1093\/sleep\/zsx154","volume":"40","author":"CM Walsh","year":"2017","unstructured":"Walsh, C. M. et al. Sleepless night and day, the plight of progressive supranuclear palsy. Sleep 40, zsx154 (2017).","journal-title":"Sleep"},{"key":"1966_CR42","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1177\/089198879901200203","volume":"12","author":"SM McCurry","year":"1999","unstructured":"McCurry, S. M. et al. Characteristics of sleep disturbance in community-dwelling Alzheimer\u2019s disease patients. J. Geriatr. Psychiatry Neurol. 12, 53\u201359 (1999).","journal-title":"J. Geriatr. Psychiatry Neurol."},{"key":"1966_CR43","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/bph.16212","volume":"181","author":"RJ Keenan","year":"2024","unstructured":"Keenan, R. J. et al. Orexin 2 receptor antagonism sex\u2010dependently improves sleep\/wakefulness and cognitive performance in tau transgenic mice. Br. J. Pharmacol. 181, 87\u2013106 (2024).","journal-title":"Br. J. Pharmacol."},{"key":"1966_CR44","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.neuron.2022.10.022","volume":"111","author":"M Gratuze","year":"2023","unstructured":"Gratuze, M. et al. TREM2-independent microgliosis promotes tau-mediated neurodegeneration in the presence of ApoE4. Neuron 111, 202\u2013219 (2023).","journal-title":"Neuron"},{"key":"1966_CR45","doi-asserted-by":"crossref","first-page":"11929","DOI":"10.1523\/JNEUROSCI.1860-14.2014","volume":"34","author":"Y Zhang","year":"2014","unstructured":"Zhang, Y. et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J. Neurosci. 34, 11929\u201311947 (2014).","journal-title":"J. Neurosci."},{"key":"1966_CR46","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1038\/s41593-019-0511-3","volume":"22","author":"YU Liu","year":"2019","unstructured":"Liu, Y. U. et al. Neuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling. Nat. Neurosci. 22, 1771\u20131781 (2019).","journal-title":"Nat. Neurosci."},{"key":"1966_CR47","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1038\/s41593-019-0514-0","volume":"22","author":"RD Stowell","year":"2019","unstructured":"Stowell, R. D. et al. Noradrenergic signaling in the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex. Nat. Neurosci. 22, 1782\u20131792 (2019).","journal-title":"Nat. Neurosci."},{"key":"1966_CR48","doi-asserted-by":"crossref","first-page":"4917","DOI":"10.1074\/jbc.M008118200","volume":"276","author":"KM Small","year":"2001","unstructured":"Small, K. M., Brown, K. M., Forbes, S. L. & Liggett, S. B. Polymorphic deletion of three intracellular acidic residues of the \u03b12B-adrenergic receptor decreases G protein-coupled receptor kinase-mediated phosphorylation and desensitization. J. Biol. Chem. 276, 4917\u20134922 (2001).","journal-title":"J. Biol. Chem."},{"key":"1966_CR49","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.ejphar.2015.05.047","volume":"761","author":"T Ijiro","year":"2015","unstructured":"Ijiro, T. et al. Effect of rovatirelin, a novel thyrotropin-releasing hormone analog, on the central noradrenergic system. Eur. J. Pharmacol. 761, 413\u2013422 (2015).","journal-title":"Eur. J. Pharmacol."},{"key":"1966_CR50","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/bph.12296","volume":"171","author":"CS Leonard","year":"2014","unstructured":"Leonard, C. S. & Kukkonen, J. P. Orexin\/hypocretin receptor signalling: a functional perspective. Br. J. Pharmacol. 171, 294\u2013313 (2014).","journal-title":"Br. J. Pharmacol."},{"key":"1966_CR51","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1111\/bph.12324","volume":"171","author":"JP Kukkonen","year":"2014","unstructured":"Kukkonen, J. P. & Leonard, C. S. Orexin\/hypocretin receptor signalling cascades. Br. J. Pharmacol. 171, 314\u2013331 (2014).","journal-title":"Br. J. Pharmacol."},{"key":"1966_CR52","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.neuroscience.2020.04.019","volume":"438","author":"H Chidambaram","year":"2020","unstructured":"Chidambaram, H. & Chinnathambi, S. G-Protein coupled receptors and tau-different roles in Alzheimer\u2019s disease. Neuroscience 438, 198\u2013214 (2020).","journal-title":"Neuroscience"},{"key":"1966_CR53","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/S0021-9258(18)54055-2","volume":"268","author":"CW Scott","year":"1993","unstructured":"Scott, C. W. et al. Phosphorylation of recombinant tau by cAMP-dependent protein kinase. Identification of phosphorylation sites and effect on microtubule assembly. J. Biol. Chem. 268, 1166\u20131173 (1993).","journal-title":"J. Biol. Chem."},{"key":"1966_CR54","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1091\/mbc.9.6.1495","volume":"9","author":"S Illenberger","year":"1998","unstructured":"Illenberger, S. et al. The endogenous and cell cycle-dependent phosphorylation of tau protein in living cells: implications for Alzheimer\u2019s disease. Mol. Biol. Cell 9, 1495\u20131512 (1998).","journal-title":"Mol. Biol. Cell"},{"key":"1966_CR55","doi-asserted-by":"crossref","first-page":"6269","DOI":"10.1016\/j.febslet.2006.10.033","volume":"580","author":"F Liu","year":"2006","unstructured":"Liu, F. et al. PKA modulates GSK\u20103\u03b2\u2010 and cdk5\u2010catalyzed phosphorylation of tau in site\u2010 and kinase\u2010specific manners. FEBS Lett. 580, 6269\u20136274 (2006).","journal-title":"FEBS Lett."},{"key":"1966_CR56","doi-asserted-by":"crossref","first-page":"6460","DOI":"10.1523\/JNEUROSCI.5018-12.2013","volume":"33","author":"J Luo","year":"2013","unstructured":"Luo, J., Phan, T. X., Yang, Y., Garelick, M. G. & Storm, D. R. Increases in cAMP, MAPK activity, and CREB phosphorylation during REM sleep: implications for REM sleep and memory consolidation. J. Neurosci. 33, 6460\u20136468 (2013).","journal-title":"J. Neurosci."},{"key":"1966_CR57","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/S0092-8674(00)81904-2","volume":"88","author":"T Abel","year":"1997","unstructured":"Abel, T. et al. Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory. Cell 88, 615\u2013626 (1997).","journal-title":"Cell"},{"key":"1966_CR58","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/nature08488","volume":"461","author":"CG Vecsey","year":"2009","unstructured":"Vecsey, C. G. et al. Sleep deprivation impairs cAMP signalling in the hippocampus. Nature 461, 1122\u20131125 (2009).","journal-title":"Nature"},{"key":"1966_CR59","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13024-019-0337-1","volume":"14","author":"T-PV Huynh","year":"2019","unstructured":"Huynh, T.-P. V. et al. Lack of hepatic apoE does not influence early A\u03b2 deposition: observations from a new APOE knock-in model. Mol. Neurodegener. 14, 37 (2019).","journal-title":"Mol. Neurodegener."},{"key":"1966_CR60","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/S0896-6273(03)00330-1","volume":"38","author":"JT Willie","year":"2003","unstructured":"Willie, J. T. et al. Distinct narcolepsy syndromes in orexin receptor-2 and orexin null mice. Neuron 38, 715\u2013730 (2003).","journal-title":"Neuron"},{"key":"1966_CR61","doi-asserted-by":"crossref","first-page":"e0224642","DOI":"10.1371\/journal.pone.0224642","volume":"14","author":"Z Barger","year":"2019","unstructured":"Barger, Z., Frye, C. G., Liu, D., Dan, Y. & Bouchard, K. E. Robust, automated sleep scoring by a compact neural network with distributional shift correction. PLoS ONE 14, e0224642 (2019).","journal-title":"PLoS ONE"},{"key":"1966_CR62","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jneumeth.2015.11.004","volume":"259","author":"F Yaghouby","year":"2016","unstructured":"Yaghouby, F., Donohue, K. D., O\u2019Hara, B. F. & Sunderam, S. Noninvasive dissection of mouse sleep using a piezoelectric motion sensor. J. Neurosci. Methods 259, 90\u2013100 (2016).","journal-title":"J. Neurosci. Methods"}],"container-title":["Nature Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41593-025-01966-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41593-025-01966-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41593-025-01966-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,6]],"date-time":"2025-07-06T22:03:08Z","timestamp":1751839388000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41593-025-01966-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,27]]},"references-count":62,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["1966"],"URL":"https:\/\/doi.org\/10.1038\/s41593-025-01966-7","relation":{},"ISSN":["1097-6256","1546-1726"],"issn-type":[{"value":"1097-6256","type":"print"},{"value":"1546-1726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,27]]},"assertion":[{"value":"23 November 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"D.M.H. is an inventor on a patent licensed by Washington University to C2N Diagnostics on the therapeutic use of anti-tau antibodies; cofounded and is on the scientific advisory board of C2N Diagnostics; is on the scientific advisory board of Denali, Genentech, Cajal Neuroscience and Switch Therapeutics and consults for Pfizer and Roche. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}