{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:31:27Z","timestamp":1786408287802,"version":"build-2736575974"},"reference-count":91,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":83,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["P30 AG066509"],"award-info":[{"award-number":["P30 AG066509"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-026-10335-4","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T06:16:24Z","timestamp":1779257784000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Diurnal choroid plexus function in mice depends on sex, age, and amyloid-\u03b2 status"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9757-8682","authenticated-orcid":false,"given":"Deidre","family":"Jansson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7698-5799","authenticated-orcid":false,"given":"Ryan","family":"O\u2019Boyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor J.","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Gino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathew","family":"Sevao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1502-1468","authenticated-orcid":false,"given":"Ron","family":"Vered","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine L.","family":"Suchland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9241-4929","authenticated-orcid":false,"given":"Blake","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8244-2624","authenticated-orcid":false,"given":"Ryann","family":"Fame","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha A.","family":"Keil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Braun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Iliff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"10335_CR1","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1126\/science.abb8739","volume":"370","author":"M Nedergaard","year":"2020","unstructured":"Nedergaard, M. & Goldman, S. A. Glymphatic failure as a final common pathway to dementia. Science 370, 50\u201356 (2020).","journal-title":"Science"},{"key":"10335_CR2","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1093\/brain\/awaa443","volume":"144","author":"PK Eide","year":"2021","unstructured":"Eide, P. K., Vinje, V., Pripp, A. H., Mardal, K.-A. & Ringstad, G. Sleep deprivation impairs molecular clearance from the human brain. Brain 144, 863\u2013874 (2021).","journal-title":"Brain"},{"key":"10335_CR3","doi-asserted-by":"publisher","first-page":"471","DOI":"10.3233\/JAD-191122","volume":"75","author":"MS Blattner","year":"2020","unstructured":"Blattner, M. S. et al. Increased cerebrospinal fluid amyloid-\u03b2 during sleep deprivation in healthy middle-aged adults is not due to stress or circadian disruption. J. Alzheimer\u2019s Dis. 75, 471\u2013482 (2020).","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"10335_CR4","doi-asserted-by":"publisher","first-page":"pgad262","DOI":"10.1093\/pnasnexus\/pgad262","volume":"2","author":"BL Edelbo","year":"2023","unstructured":"Edelbo, B. L., Andreassen, S. N., Steffensen, A. B. & MacAulay, N. Day\u2013night fluctuations in choroid plexus transcriptomics and cerebrospinal fluid metabolomics. PNAS Nexus 2, pgad262 (2023).","journal-title":"PNAS Nexus"},{"key":"10335_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39326-3","volume":"14","author":"RM Fame","year":"2023","unstructured":"Fame, R. M. et al. Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution. Nat. Commun. 14, 3720 (2023).","journal-title":"Nat. Commun."},{"key":"10335_CR6","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.13522","volume":"31","author":"M Forsberg","year":"2022","unstructured":"Forsberg, M. et al. Ion concentrations in cerebrospinal fluid in wakefulness, sleep and sleep deprivation in healthy humans. J. Sleep Res. 31, e13522 (2022).","journal-title":"J. Sleep Res."},{"key":"10335_CR7","doi-asserted-by":"publisher","first-page":"R20","DOI":"10.1152\/ajpregu.1992.262.1.R20","volume":"262","author":"C Nilsson","year":"1992","unstructured":"Nilsson, C. et al. Circadian variation in human cerebrospinal fluid production measured by magnetic resonance imaging. Am. J. Physiol.-Regul. Integr. Comp. Physiol. 262, R20\u2013R24 (1992).","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"10335_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-020-18115-2","volume":"11","author":"LM Hablitz","year":"2020","unstructured":"Hablitz, L. M. et al. Circadian control of brain glymphatic and lymphatic fluid flow. Nat. Commun. 11, 1\u201311 (2020).","journal-title":"Nat. Commun."},{"key":"10335_CR9","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1126\/science.1241224","volume":"342","author":"L Xie","year":"2013","unstructured":"Xie, L. et al. Sleep drives metabolite clearance from the adult brain. Science 342, 373\u2013377 (2013).","journal-title":"Science"},{"key":"10335_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03507-2","volume":"9","author":"J Myung","year":"2018","unstructured":"Myung, J. et al. The choroid plexus is an important circadian clock component. Nat. Commun. 9, 1062 (2018).","journal-title":"Nat. Commun."},{"key":"10335_CR11","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.bbi.2015.06.008","volume":"49","author":"SD Mesquita","year":"2015","unstructured":"Mesquita, S. D. et al. The choroid plexus transcriptome reveals changes in type I and II interferon responses in a mouse model of Alzheimer\u2019s disease. Brain Behav. Immun. 49, 280\u2013292 (2015).","journal-title":"Brain Behav. Immun."},{"key":"10335_CR12","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1002\/jnr.25164","volume":"101","author":"A Furtado","year":"2023","unstructured":"Furtado, A. et al. Circadian rhythmicity of amyloid-beta-related molecules is disrupted in the choroid plexus of a female Alzheimer\u2019s disease mouse model. J. Neurosci. Res. 101, 524\u2013540 (2023).","journal-title":"J. Neurosci. Res."},{"key":"10335_CR13","doi-asserted-by":"publisher","first-page":"3537","DOI":"10.1002\/alz.12970","volume":"19","author":"M \u010carna","year":"2023","unstructured":"\u010carna, M. et al. Pathogenesis of Alzheimer\u2019s disease: involvement of the choroid plexus. Alzheimer\u2019s Dement. 19, 3537\u20133554 (2023).","journal-title":"Alzheimer\u2019s Dement."},{"key":"10335_CR14","doi-asserted-by":"publisher","first-page":"3056","DOI":"10.1016\/j.cell.2021.04.003","volume":"184","author":"N Dani","year":"2021","unstructured":"Dani, N. et al. A cellular and spatial map of the choroid plexus across brain ventricles and ages. Cell 184, 3056\u20133074. e3021 (2021).","journal-title":"Cell"},{"key":"10335_CR15","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3389\/fncel.2015.00017","volume":"9","author":"I Gonz\u00e1lez-Marrero","year":"2015","unstructured":"Gonz\u00e1lez-Marrero, I. et al. Choroid plexus dysfunction impairs beta-amyloid clearance in a triple transgenic mouse model of Alzheimer\u2019s disease. Front. Cell. Neurosci. 9, 17 (2015).","journal-title":"Front. Cell. Neurosci."},{"key":"10335_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12987-018-0102-9","volume":"15","author":"EG Stopa","year":"2018","unstructured":"Stopa, E. G. et al. Comparative transcriptomics of choroid plexus in Alzheimer\u2019s disease, frontotemporal dementia and Huntington\u2019s disease: implications for CSF homeostasis. Fluids Barriers CNS 15, 1\u201310 (2018).","journal-title":"Fluids Barriers CNS"},{"key":"10335_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12864-015-2159-z","volume":"16","author":"AA Bergen","year":"2015","unstructured":"Bergen, A. A. et al. Gene expression and functional annotation of human choroid plexus epithelium failure in Alzheimer\u2019s disease. BMC Genom. 16, 1\u201315 (2015).","journal-title":"BMC Genom."},{"key":"10335_CR18","doi-asserted-by":"publisher","first-page":"505","DOI":"10.3233\/JAD-2011-101959","volume":"25","author":"S Chalbot","year":"2011","unstructured":"Chalbot, S. et al. Blood-cerebrospinal fluid barrier permeability in Alzheimer\u2019s disease. J. Alzheimer\u2019s Dis. 25, 505\u2013515 (2011).","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"10335_CR19","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1111\/j.1749-6632.1997.tb48514.x","volume":"826","author":"J Serot","year":"1997","unstructured":"Serot, J., Bene, M., Foliguet, B. & Faure, G. Altered choroid plexus basement membrane and epithelium in late-onset Alzheimer\u2019s disease: an ultrastructural study. Ann. N. Y. Acad. Sci. 826, 507\u2013509 (1997).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10335_CR20","doi-asserted-by":"publisher","first-page":"1221775","DOI":"10.3389\/fneur.2023.1221775","volume":"14","author":"DF Leitner","year":"2023","unstructured":"Leitner, D. F., Kanshin, E., Faustin, A. & Wisniewski, T. Localized proteomic differences in the choroid plexus of Alzheimer\u2019s disease and epilepsy patients. Front. Neurol. 14, 1221775 (2023).","journal-title":"Front. Neurol."},{"key":"10335_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12883-020-01849-3","volume":"20","author":"A Pearson","year":"2020","unstructured":"Pearson, A. et al. Molecular abnormalities in autopsied brain tissue from the inferior horn of the lateral ventricles of nonagenarians and Alzheimer disease patients. BMC Neurol. 20, 1\u201320 (2020).","journal-title":"BMC Neurol."},{"key":"10335_CR22","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.neurobiolaging.2020.01.005","volume":"89","author":"E Tadayon","year":"2020","unstructured":"Tadayon, E., Pascual-Leone, A., Press, D., Santarnecchi, E. & Initiative, A.sD. N. Choroid plexus volume is associated with levels of CSF proteins: relevance for Alzheimer\u2019s and Parkinson\u2019s disease. Neurobiol. Aging 89, 108\u2013117 (2020).","journal-title":"Neurobiol. Aging"},{"key":"10335_CR23","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.734992","volume":"13","author":"JS Alisch","year":"2021","unstructured":"Alisch, J. S. et al. Characterization of age-related differences in the human choroid plexus volume, microstructural integrity, and blood perfusion using multiparameter magnetic resonance imaging. Front. Aging Neurosci. 13, 734992 (2021).","journal-title":"Front. Aging Neurosci."},{"key":"10335_CR24","unstructured":"Jeong, S. H. et al. Choroid plexus volume, amyloid burden, and cognition in the Alzheimer\u2019s disease continuum. Aging Dis.16,1 (2024)."},{"key":"10335_CR25","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1212\/WNL.40.3_Part_1.500","volume":"40","author":"C May","year":"1990","unstructured":"May, C. et al. Cerebrospinal fluid production is reduced in healthy aging. Neurology 40, 500\u2013500 (1990).","journal-title":"Neurology"},{"key":"10335_CR26","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1212\/WNL.57.10.1763","volume":"57","author":"G Silverberg","year":"2001","unstructured":"Silverberg, G. et al. The cerebrospinal fluid production rate is reduced in dementia of the Alzheimer\u2019s type. Neurology 57, 1763\u20131766 (2001).","journal-title":"Neurology"},{"key":"10335_CR27","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1016\/S1474-4422(03)00487-3","volume":"2","author":"GD Silverberg","year":"2003","unstructured":"Silverberg, G. D., Mayo, M., Saul, T., Rubenstein, E. & McGuire, D. Alzheimer\u2019s disease, normal-pressure hydrocephalus, and senescent changes in CSF circulatory physiology: a hypothesis.  Lancet Neurol. 2, 506\u2013511 (2003).","journal-title":"Lancet Neurol."},{"key":"10335_CR28","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1073\/pnas.1508249112","volume":"113","author":"C-Y Chen","year":"2016","unstructured":"Chen, C.-Y. et al. Effects of aging on circadian patterns of gene expression in the human prefrontal cortex. Proc. Natl. Acad. Sci. USA 113, 206\u2013211 (2016).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10335_CR29","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.5665\/sleep.2802","volume":"36","author":"AS Lim","year":"2013","unstructured":"Lim, A. S., Kowgier, M., Yu, L., Buchman, A. S. & Bennett, D. A. Sleep fragmentation and the risk of incident Alzheimer\u2019s disease and cognitive decline in older persons. Sleep 36, 1027\u20131032 (2013).","journal-title":"Sleep"},{"key":"10335_CR30","doi-asserted-by":"publisher","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":"10335_CR31","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1016\/j.sleep.2012.10.009","volume":"14","author":"CH Schenck","year":"2013","unstructured":"Schenck, C. H., Boeve, B. F. & Mahowald, M. W. Delayed emergence of a Parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Med. 14, 744\u2013748 (2013).","journal-title":"Sleep Med."},{"key":"10335_CR32","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1002\/ana.22468","volume":"70","author":"GJ Tranah","year":"2011","unstructured":"Tranah, G. J. et al. Circadian activity rhythms and risk of incident dementia and mild cognitive impairment in older women. Ann. Neurol. 70, 722\u2013732 (2011).","journal-title":"Ann. Neurol."},{"key":"10335_CR33","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1001\/jamaneurol.2016.4370","volume":"74","author":"DM Zeppenfeld","year":"2017","unstructured":"Zeppenfeld, D. M. et al. Association of perivascular localization of aquaporin-4 with cognition and Alzheimer disease in aging brains. JAMA Neurol. 74, 91\u201399 (2017).","journal-title":"JAMA Neurol."},{"key":"10335_CR34","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1002\/ana.24271","volume":"76","author":"BT Kress","year":"2014","unstructured":"Kress, B. T. et al. Impairment of paravascular clearance pathways in the aging brain. Ann. Neurol. 76, 845\u2013861 (2014).","journal-title":"Ann. Neurol."},{"key":"10335_CR35","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1038\/nrg2430","volume":"9","author":"JS Takahashi","year":"2008","unstructured":"Takahashi, J. S., Hong, H.-K., Ko, C. H. & McDearmon, E. L. The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nat. Rev. Genet. 9, 764\u2013775 (2008).","journal-title":"Nat. Rev. Genet."},{"key":"10335_CR36","doi-asserted-by":"crossref","unstructured":"Venkatesan, A., Satin, L. S. & Raghavan, M. In Cellular Biology of the Endoplasmic Reticulum, (ed. Agellon, L. & Michalak, M.) 145\u2013162 (Springer, 2021).","DOI":"10.1007\/978-3-030-67696-4_7"},{"key":"10335_CR37","doi-asserted-by":"publisher","first-page":"1742","DOI":"10.1158\/0008-5472.CAN-10-3453","volume":"71","author":"L Qin","year":"2011","unstructured":"Qin, L. et al. Steroid receptor coactivator-1 upregulates integrin \u03b15 expression to promote breast cancer cell adhesion and migration. Cancer Res. 71, 1742\u20131751 (2011).","journal-title":"Cancer Res."},{"key":"10335_CR38","doi-asserted-by":"publisher","first-page":"8695","DOI":"10.1007\/s12035-018-0998-8","volume":"55","author":"H Kumar","year":"2018","unstructured":"Kumar, H., Lee, S.-H., Kim, K.-T., Zeng, X. & Han, I. TRPV4: a sensor for homeostasis and pathological events in the CNS. Mol. Neurobiol. 55, 8695\u20138708 (2018).","journal-title":"Mol. Neurobiol."},{"key":"10335_CR39","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.tins.2017.11.003","volume":"41","author":"J-P Changeux","year":"2018","unstructured":"Changeux, J.-P. Structural identification of the nicotinic receptor ion channel. Trends Neurosci. 41, 67\u201370 (2018).","journal-title":"Trends Neurosci."},{"key":"10335_CR40","doi-asserted-by":"publisher","first-page":"2615","DOI":"10.1007\/s11064-015-1519-z","volume":"40","author":"M Assentoft","year":"2015","unstructured":"Assentoft, M., Larsen, B. R. & MacAulay, N. Regulation and function of AQP4 in the central nervous system. Neurochem. Res. 40, 2615\u20132627 (2015).","journal-title":"Neurochem. Res."},{"key":"10335_CR41","doi-asserted-by":"publisher","first-page":"F972","DOI":"10.1152\/ajprenal.00356.2003","volume":"286","author":"D Sykes","year":"2004","unstructured":"Sykes, D. et al. Organic anion transport in choroid plexus from wild-type and organic anion transporter 3 (Slc22a8)-null mice. Am. J. Physiol.-Ren. Physiol. 286, F972\u2013F978 (2004).","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"10335_CR42","doi-asserted-by":"publisher","DOI":"10.1038\/srep31603","volume":"6","author":"A Didonna","year":"2016","unstructured":"Didonna, A., Cekanaviciute, E., Oksenberg, J. R. & Baranzini, S. E. Immune cell-specific transcriptional profiling highlights distinct molecular pathways controlled by Tob1 upon experimental autoimmune encephalomyelitis. Sci. Rep. 6, 31603 (2016).","journal-title":"Sci. Rep."},{"key":"10335_CR43","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1172\/JCI90328","volume":"127","author":"S Hood","year":"2017","unstructured":"Hood, S. & Amir, S. The aging clock: circadian rhythms and later life.  J. Clin. Investig. 127, 437\u2013446 (2017).","journal-title":"J. Clin. Investig."},{"key":"10335_CR44","doi-asserted-by":"publisher","first-page":"E11388","DOI":"10.1073\/pnas.1808609115","volume":"115","author":"L Zhu","year":"2018","unstructured":"Zhu, L. et al. Klotho controls the brain\u2013immune system interface in the choroid plexus. Proc. Natl. Acad. Sci. USA 115, E11388\u2013E11396 (2018).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10335_CR45","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1126\/science.1252945","volume":"346","author":"K Baruch","year":"2014","unstructured":"Baruch, K. et al. Aging-induced type I interferon response at the choroid plexus negatively affects brain function. Science 346, 89\u201393 (2014).","journal-title":"Science"},{"key":"10335_CR46","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/PL00007412","volume":"99","author":"J-M Serot","year":"2000","unstructured":"Serot, J.-M., B\u00e9n\u00e9, M.-C., Foliguet, B. & Faure, G. C. Morphological alterations of the choroid plexus in late-onset Alzheimer\u2019s disease. Acta Neuropathol. 99, 105\u2013108 (2000).","journal-title":"Acta Neuropathol."},{"key":"10335_CR47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12987-018-0120-7","volume":"15","author":"S Kant","year":"2018","unstructured":"Kant, S., Stopa, E. G., Johanson, C. E., Baird, A. & Silverberg, G. D. Choroid plexus genes for CSF production and brain homeostasis are altered in Alzheimer\u2019s disease. Fluids Barriers CNS 15, 1\u201310 (2018).","journal-title":"Fluids Barriers CNS"},{"key":"10335_CR48","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsaa087","volume":"43","author":"MJ Filon","year":"2020","unstructured":"Filon, M. J. et al. Sleep and diurnal rest-activity rhythm disturbances in a mouse model of Alzheimer\u2019s disease. Sleep 43, zsaa087 (2020).","journal-title":"Sleep"},{"key":"10335_CR49","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1096\/fj.04-1711fje","volume":"19","author":"K Oshio","year":"2005","unstructured":"Oshio, K., Watanabe, H., Song, Y., Verkman, A. & Manley, G. T. Reduced cerebrospinal fluid production and intracranial pressure in mice lacking choroid plexus water channel Aquaporin-1.  FASEB J. 19, 76\u201378 (2005).","journal-title":"FASEB J."},{"key":"10335_CR50","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202409120","volume":"12","author":"DB Jensen","year":"2025","unstructured":"Jensen, D. B. et al. The Na+, K+, 2Cl\u2212 cotransporter, not aquaporin 1, sustains cerebrospinal fluid secretion while controlling brain K+ homeostasis. Adv. Sci. 12, 2409120 (2025).","journal-title":"Adv. Sci."},{"key":"10335_CR51","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-023-00829-w","volume":"24","author":"IME Israelsen","year":"2023","unstructured":"Israelsen, I. M. E. et al. Cycle-dependent sex differences in expression of membrane proteins involved in cerebrospinal fluid secretion at rat choroid plexus. BMC Neurosci. 24, 60 (2023).","journal-title":"BMC Neurosci."},{"key":"10335_CR52","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-023-00451-2","volume":"20","author":"AB Steffensen","year":"2023","unstructured":"Steffensen, A. B. et al. Nocturnal increase in cerebrospinal fluid secretion as a circadian regulator of intracranial pressure. Fluids Barriers CNS 20, 49 (2023).","journal-title":"Fluids Barriers CNS"},{"key":"10335_CR53","doi-asserted-by":"crossref","unstructured":"Sheehan, P. W. et al. A glial circadian gene expression atlas reveals cell-type and disease-specific reprogramming in response to amyloid pathology or aging. Nat. Neurosci. 28, 1\u201314 (2025).","DOI":"10.1038\/s41593-025-02067-1"},{"key":"10335_CR54","doi-asserted-by":"publisher","first-page":"1218193","DOI":"10.3389\/fnagi.2023.1218193","volume":"15","author":"TK Weigel","year":"2023","unstructured":"Weigel, T. K., Guo, C. L., G\u00fcler, A. D. & Ferris, H. A. Altered circadian behavior and light sensing in mouse models of Alzheimer\u2019s disease. Front. Aging Neurosci. 15, 1218193 (2023).","journal-title":"Front. Aging Neurosci."},{"key":"10335_CR55","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1177\/153537020523001011","volume":"230","author":"JS Crossgrove","year":"2005","unstructured":"Crossgrove, J. S., Li, G. J. & Zheng, W. The choroid plexus removes \u03b2-amyloid from brain cerebrospinal fluid. Exp. Biol. Med. 230, 771\u2013776 (2005).","journal-title":"Exp. Biol. Med."},{"key":"10335_CR56","doi-asserted-by":"publisher","first-page":"4229","DOI":"10.1073\/pnas.93.9.4229","volume":"93","author":"BV Zlokovic","year":"1996","unstructured":"Zlokovic, B. V. et al. Glycoprotein 330\/megalin: probable role in receptor-mediated transport of apolipoprotein J alone and in a complex with Alzheimer disease amyloid beta at the blood\u2013brain and blood\u2013cerebrospinal fluid barriers. Proc. Natl. Acad. Sci. USA 93, 4229\u20134234 (1996).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10335_CR57","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1126\/science.1180962","volume":"326","author":"J-E 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":"10335_CR58","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1084\/jem.20172347","volume":"215","author":"GJ Kress","year":"2018","unstructured":"Kress, G. J. et al. Regulation of amyloid-\u03b2 dynamics and pathology by the circadian clock. J. Exp. Med. 215, 1059\u20131068 (2018).","journal-title":"J. Exp. Med."},{"key":"10335_CR59","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1001\/archneurol.2012.18107","volume":"69","author":"Y Huang","year":"2012","unstructured":"Huang, Y. et al. \u03b2-Amyloid dynamics in human plasma. Arch. Neurol. 69, 1591\u20131597 (2012).","journal-title":"Arch. Neurol."},{"key":"10335_CR60","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1016\/j.cell.2017.07.042","volume":"170","author":"S Sato","year":"2017","unstructured":"Sato, S. et al. Circadian reprogramming in the liver identifies metabolic pathways of aging. Cell 170, 664\u2013677 e611 (2017).","journal-title":"Cell"},{"key":"10335_CR61","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14529","volume":"8","author":"RC Kuintzle","year":"2017","unstructured":"Kuintzle, R. C. et al. Circadian deep sequencing reveals stress-response genes that adopt robust rhythmic expression during aging. Nat. Commun. 8, 14529 (2017).","journal-title":"Nat. Commun."},{"key":"10335_CR62","doi-asserted-by":"publisher","first-page":"3661","DOI":"10.1016\/j.jmb.2019.12.036","volume":"432","author":"P-S Welz","year":"2020","unstructured":"Welz, P.-S. & Benitah, S. Molecular connections between circadian clocks and aging. J. Mol. Biol. 432, 3661\u20133679 (2020).","journal-title":"J. Mol. Biol."},{"key":"10335_CR63","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-61889-6","volume":"16","author":"SD Lolansen","year":"2025","unstructured":"Lolansen, S. D. et al. Choroid plexus-mediated CSF secretion remains stable in aging rats via high and age-resistant metabolic activity. Nat. Commun. 16, 6778 (2025).","journal-title":"Nat. Commun."},{"key":"10335_CR64","first-page":"251","volume":"26","author":"T Kleine","year":"1993","unstructured":"Kleine, T., Hackler, R., L\u00fctcke, A., Dauch, W. & Z\u00f6fel, P. Transport and production of cerebrospinal fluid (CSF) change in aging humans under normal and diseased conditions. Z. Gerontol. 26, 251\u2013255 (1993).","journal-title":"Z. Gerontol."},{"key":"10335_CR65","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1007\/s00429-014-0720-1","volume":"220","author":"T Quintela","year":"2015","unstructured":"Quintela, T., Sousa, C., Patriarca, F., Gon\u00e7alves, I. & Santos, C. Gender associated circadian oscillations of the clock genes in rat choroid plexus. Brain Struct. Funct. 220, 1251\u20131262 (2015).","journal-title":"Brain Struct. Funct."},{"key":"10335_CR66","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1080\/07420528.2017.1400978","volume":"35","author":"T Quintela","year":"2018","unstructured":"Quintela, T. et al. The choroid plexus harbors a circadian oscillator modulated by estrogens. Chronobiol. Int. 35, 270\u2013279 (2018).","journal-title":"Chronobiol. Int."},{"key":"10335_CR67","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.neulet.2013.07.038","volume":"552","author":"J Murgu\u00eda-Castillo","year":"2013","unstructured":"Murgu\u00eda-Castillo, J., Beas-Z\u00e1rate, C., Rivera-Cervantes, M. C., Feria-Velasco, A. I. & Ure\u00f1a-Guerrero, M. E. NKCC1 and KCC2 protein expression is sexually dimorphic in the hippocampus and entorhinal cortex of neonatal rats. Neurosci. Lett. 552, 52\u201357 (2013).","journal-title":"Neurosci. Lett."},{"key":"10335_CR68","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1212\/01.wnl.0000333254.84120.f5","volume":"72","author":"B Bruce","year":"2009","unstructured":"Bruce, B. et al. Idiopathic intracranial hypertension in men. Neurology 72, 304\u2013309 (2009).","journal-title":"Neurology"},{"key":"10335_CR69","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/alz.12328","volume":"17","author":"J Wiley","year":"2021","unstructured":"Wiley, J. Alzheimer\u2019s disease facts and figures. Alzheimers Dement. 17, 327\u2013406 (2021).","journal-title":"Alzheimers Dement."},{"key":"10335_CR70","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1002\/alz.12362","volume":"17","author":"KB Rajan","year":"2021","unstructured":"Rajan, K. B. et al. Population estimate of people with clinical Alzheimer's disease and mild cognitive impairment in the United States (2020\u20132060). Alzheimer\u2019s Dement. 17, 1966\u20131975 (2021).","journal-title":"Alzheimer\u2019s Dement."},{"key":"10335_CR71","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2023.1039239","volume":"14","author":"J Novakova Martinkova","year":"2023","unstructured":"Novakova Martinkova, J. et al. Longitudinal progression of choroid plexus enlargement is associated with female sex, cognitive decline and ApoE E4 homozygote status. Front. Psychiatry 14, 1039239 (2023).","journal-title":"Front. Psychiatry"},{"key":"10335_CR72","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/j.stem.2016.06.013","volume":"19","author":"V Silva-Vargas","year":"2016","unstructured":"Silva-Vargas, V., Maldonado-Soto, A. R., Mizrak, D., Codega, P. & Doetsch, F. Age-dependent niche signals from the choroid plexus regulate adult neural stem cells. Cell Stem Cell 19, 643\u2013652 (2016).","journal-title":"Cell Stem Cell"},{"key":"10335_CR73","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.tins.2024.05.010","volume":"47","author":"A Tsitsou-Kampeli","year":"2024","unstructured":"Tsitsou-Kampeli, A., Suzzi, S. & Schwartz, M. The immune and metabolic milieu of the choroid plexus as a potential target in brain protection. Trends Neurosci. 47, 573\u2013582 (2024).","journal-title":"Trends Neurosci."},{"key":"10335_CR74","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-023-00438-z","volume":"20","author":"RM Fame","year":"2023","unstructured":"Fame, R. M., Xu, H., Pragana, A. & Lehtinen, M. Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1. Fluids Barriers CNS 20, 45 (2023).","journal-title":"Fluids Barriers CNS"},{"key":"10335_CR75","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13334","volume":"20","author":"A Popov","year":"2021","unstructured":"Popov, A. et al. Astrocyte dystrophy in ageing brain parallels impaired synaptic plasticity. Aging Cell 20, e13334 (2021).","journal-title":"Aging Cell"},{"key":"10335_CR76","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.neubiorev.2017.03.002","volume":"77","author":"A Bellot-Saez","year":"2017","unstructured":"Bellot-Saez, A., K\u00e9kesi, O., Morley, J. W. & Buskila, Y. Astrocytic modulation of neuronal excitability through K+ spatial buffering. Neurosci. Biobehav. Rev. 77, 87\u201397 (2017).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10335_CR77","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2305071120","volume":"120","author":"AG Dietz","year":"2023","unstructured":"Dietz, A. G. et al. Local extracellular K+ in cortex regulates norepinephrine levels, network state, and behavioral output. Proc. Natl. Acad. Sci. USA 120, e2305071120 (2023).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10335_CR78","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1016\/j.celrep.2019.06.082","volume":"28","author":"R Rasmussen","year":"2019","unstructured":"Rasmussen, R. et al. Cortex-wide changes in extracellular potassium ions parallel brain state transitions in awake behaving mice. Cell Rep. 28, 1182\u20131194 e1184 (2019).","journal-title":"Cell Rep."},{"key":"10335_CR79","doi-asserted-by":"publisher","first-page":"2983","DOI":"10.1016\/j.cub.2019.07.056","volume":"29","author":"CM Muheim","year":"2019","unstructured":"Muheim, C. M. et al. Dynamic-and frequency-specific regulation of sleep oscillations by cortical potassium channels. Curr. Biol. 29, 2983\u20132992 e2983 (2019).","journal-title":"Curr. Biol."},{"key":"10335_CR80","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaf201","volume":"7","author":"T Lyckenvik","year":"2025","unstructured":"Lyckenvik, T. et al. Ion concentrations in CSF and serum are differentially and precisely regulated. Brain Commun. 7, fcaf201 (2025).","journal-title":"Brain Commun."},{"key":"10335_CR81","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/0165-3806(91)90051-J","volume":"60","author":"JT Parmelee","year":"1991","unstructured":"Parmelee, J. T., Bairamian, D. & Johanson, C. E. Response of infant and adult rat choroid plexus potassium transporters to increased extracellular potassium. Dev. Brain Res. 60, 229\u2013233 (1991).","journal-title":"Dev. Brain Res."},{"key":"10335_CR82","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1093\/brain\/awae075","volume":"147","author":"F Ding","year":"2024","unstructured":"Ding, F. et al. Dysregulation of extracellular potassium distinguishes healthy ageing from neurodegeneration. Brain 147, 1726\u20131739 (2024).","journal-title":"Brain"},{"key":"10335_CR83","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20795-9","volume":"12","author":"SL Zhang","year":"2021","unstructured":"Zhang, S. L. et al. A circadian clock regulates efflux by the blood\u2013brain barrier in mice and human cells. Nat. Commun. 12, 617 (2021).","journal-title":"Nat. Commun."},{"key":"10335_CR84","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.867070","volume":"13","author":"V Mastrullo","year":"2022","unstructured":"Mastrullo, V. et al. Pericytes\u2019 circadian clock affects endothelial cells\u2019 synchronization and angiogenesis in a 3D tissue engineered scaffold. Front. Pharmacol. 13, 867070 (2022).","journal-title":"Front. Pharmacol."},{"key":"10335_CR85","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1177\/19714009211002778","volume":"34","author":"N Mokhber","year":"2021","unstructured":"Mokhber, N. et al. Cerebral blood flow changes during aging process and in cognitive disorders: a review.  Neuroradiol. J. 34, 300\u2013307 (2021).","journal-title":"Neuroradiol. J."},{"key":"10335_CR86","doi-asserted-by":"publisher","first-page":"e13796","DOI":"10.1111\/psyp.13796","volume":"58","author":"B Zimmerman","year":"2021","unstructured":"Zimmerman, B., Rypma, B., Gratton, G. & Fabiani, M. Age-related changes in cerebrovascular health and their effects on neural function and cognition: a comprehensive review. Psychophysiology 58, e13796 (2021).","journal-title":"Psychophysiology"},{"key":"10335_CR87","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.expneurol.2015.02.032","volume":"267","author":"R Spector","year":"2015","unstructured":"Spector, R., Keep, R. F., Snodgrass, S. R., Smith, Q. R. & Johanson, C. E. A balanced view of choroid plexus structure and function: focus on adult humans. Exp. Neurol. 267, 78\u201386 (2015).","journal-title":"Exp. Neurol."},{"key":"10335_CR88","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1055\/s-0046-1820471","volume":"2","author":"V Ramesh","year":"2009","unstructured":"Ramesh, V. & Gozal, D. Sleep fragmentation differentially modifies EEG delta power during slow wave sleep in socially isolated and paired mice. Slee. Sci. 2, 64\u201375 (2009).","journal-title":"Slee. Sci."},{"key":"10335_CR89","doi-asserted-by":"crossref","unstructured":"Wang, C. et al. APOE-\u03b54 synergizes with sleep disruption to accelerate A\u03b2 deposition and A\u03b2-associated tau seeding and spreading. J. Clin. Investig. 133, 14 (2023).","DOI":"10.1172\/JCI169131"},{"key":"10335_CR90","doi-asserted-by":"publisher","first-page":"W395","DOI":"10.1093\/nar\/gkaa434","volume":"48","author":"V Jalili","year":"2020","unstructured":"Jalili, V. et al. The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2020 update. Nucleic Acids Res. 48, W395\u2013W402 (2020).","journal-title":"Nucleic Acids Res."},{"key":"10335_CR91","doi-asserted-by":"publisher","unstructured":"Jansson, D. Jansson_et_al_Choroid_plexus_circadian_analysis. figshare. Online resource. https:\/\/doi.org\/10.6084\/m9.figshare.32129572 (2026).","DOI":"10.6084\/m9.figshare.32129572"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10335-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10335-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10335-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:03:27Z","timestamp":1786406607000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10335-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":91,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["10335"],"URL":"https:\/\/doi.org\/10.1038\/s42003-026-10335-4","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]},"assertion":[{"value":"19 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"J.J.I. serves as the Chair of the Scientific Advisory Board for Applied Cognition, Inc., from which he receives compensation and in which he holds an equity stake. The other authors have no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"All authors have consented to the publication of this manuscript.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"1073"}}