The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans
Open accessPublished version of a preprint
Abstract
Sleep may protect the brain from AD: Two main proteins accumulate in the brain in Alzheimer's disease (AD), β-amyloid (Aβ) and tau. Aβ appears to instigate AD, but tau appears to drive brain damage and cognitive decline. Sleep deprivation is known to increase Aβ acutely and chronically. Now, Holth et al. show that chronic sleep deprivation strongly increases tau acutely over hours and also drives tau pathology spreading in the brains of mice and humans (see the Perspective by Noble and Spires-Jones). Thus, sleep appears to have a direct protective effect on a key protein that drives AD pathology. Science , this issue p. 880 ; see also p. 813
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Chronic sleep deprivation enhances Aβ plaque deposition and pathological tau spreading in mice.
“Chronic sleep deprivation was shown to enhance Aβ plaque deposition and pathological tau spreading in mice [420].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [420]
Tau levels in mouse ISF and human CSF are higher during normal wakefulness versus sleep; chronic SD increases pathological tau spreading in mice; chemogenetic induction of wake states in mice increases both ISF Aβ and tau.
“A recent study shows that tau levels in mouse ISF and human CSF are higher during normal wakefulness versus sleep. Chronic SD increases pathological tau spreading in mice. In addition, chemogenetic induction of wake states in mice significantly increases both ISF Aβ and tau [420].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [420]
Amyloid-β, tau, and α-synuclein are present at higher levels in brain extracellular fluid and CSF during wakefulness than sleep; sleep deprivation increases their levels further.
“amyloid-ß, tau and α-synuclein are all present at higher levels in the brain extracellular fluid and CSF during wakefulness than during sleep, and sleep deprivation increases their levels further (106–108).”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [108]
Recent neuroimaging advances provide approaches to map the human glymphatic system and assess its functional competence in disease and effects on sleep-dependent glymphatic cyclicity.
“In that regard, recent advances in neuroimaging have provided multiple approaches to map the human glymphatic system, and hence to assess its functional competence in the context of disease, as well as of the effects thereof on sleep-dependent glymphatic cyclicity (72, 73, 108).”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [108]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Sleep Drives Metabolite Clearance from the Adult Brain
Xie, L., Kang, H., Xu, Q., Chen, M. J., Liao, Y., Thiyagarajan, M., O’Donnell, J., Christensen, D. J., Nicholson, C., Iliff, J. J., et al. (2013) · Science · doi:10.1126/science.1241224 · Cited by 5,411 · see citing works
Transmission and spreading of tauopathy in transgenic mouse brain
Clavaguera, F., Bolmont, T., Crowther, R. A., Abramowski, D., Frank, S., Probst, A., Fraser, G., Stalder, A. K., Beibel, M., Staufenbiel, M., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1901 · Cited by 1,803 · see citing works
Jankowsky, J. L., Fadale, D. J., Anderson, J., Xu, G. M., Gonzales, V., Jenkins, N. A., Copeland, N. G., Lee, M. K., Younkin, L. H., Wagner, S. L., et al. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh019 · Cited by 1,575 · see citing works
Amyloid-β Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle
Kang, J.-E., Lim, M. M., Bateman, R. J., Lee, J. J., Smyth, L. P., Cirrito, J. R., Fujiki, N., Nishino, S., & Holtzman, D. M. (2009) · Science · doi:10.1126/science.1180962 · Cited by 1,565 · see citing works
Self-citationPropagation of Tau Pathology in a Model of Early Alzheimer's Disease
de Calignon, A., Polydoro, M., Suárez-Calvet, M., William, C., Adamowicz, D. H., Kopeikina, K. J., Pitstick, R., Sahara, N., Ashe, K. H., Carlson, G. A., et al. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.033 · Cited by 1,427 · see citing works
Tau pathology and neurodegeneration
Spillantini, M. G., & Goedert, M. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70090-5 · Cited by 1,133 · see citing works
Trans-Synaptic Spread of Tau Pathology In Vivo
Liu, L., Drouet, V., Wu, J., Witter, M. P., Small, S. A., Clelland, C. L. T., & Duff, K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031302 · Cited by 994 · see citing works
Neuronal activity regulates the regional vulnerability to amyloid-β deposition
Bero, A. W., Yan, P., Roh, J. H., Cirrito, J. R., Stewart, F. R., Raichle, M. E., Lee, J.-M., & Holtzman, D. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2801 · Cited by 880 · see citing works
Self-citationVyazovskiy, V. V., Cirelli, C., Pfister-Genskow, M., Faraguna, U., & Tononi, G. (2008) · Nature Neuroscience · doi:10.1038/nn2035 · Cited by 837 · cited 1× · see citing works
“As neuronal synaptic strength/connectivity is higher during wakefulness than during sleep (11, 12), we asked whether tau levels in the brain interstitial fluid (ISF) varied with the sleep-wake cycle.”
BackgroundNeuronal activity enhances tau propagation and tau pathology in vivo
Wu, J. W., Hussaini, S. A., Bastille, I. M., Rodriguez, G. A., Mrejeru, A., Rilett, K., Sanders, D. W., Cook, C., Fu, H., Boonen, R. A. C. M., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4328 · Cited by 820 · see citing works
Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer’s disease
Bejanin, A., Schonhaut, D. R., La Joie, R., Kramer, J. H., Baker, S. L., Sosa, N., Ayakta, N., Cantwell, A., Janabi, M., Lauriola, M., et al. (2017) · Brain · doi:10.1093/brain/awx243 · Cited by 778 · see citing works
Prion-like mechanisms in neurodegenerative diseases
Frost, B., & Diamond, M. I. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2786 · Cited by 776 · see citing works
Iba, M., Guo, J. L., McBride, J. D., Zhang, B., Trojanowski, J. Q., & Lee, V. M.-Y. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.2642-12.2013 · Cited by 664 · see citing works
Physiological release of endogenous tau is stimulated by neuronal activity
Pooler, A. M., Phillips, E. C., Lau, D. H. W., Noble, W., & Hanger, D. P. (2013) · The EMBO Reports · doi:10.1038/embor.2013.15 · Cited by 642 · see citing works
Tau Kinetics in Neurons and the Human Central Nervous System
Sato, C., Barthélemy, N. R., Mawuenyega, K. G., Patterson, B. W., Gordon, B. A., Jockel-Balsarotti, J., Sullivan, M., Crisp, M. J., Kasten, T., Kirmess, K. M., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.02.015 · Cited by 586 · see citing works
Yanamandra, K., Kfoury, N., Jiang, H., Mahan, T. E., Ma, S., Maloney, S. E., Wozniak, D. F., Diamond, M. I., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.046 · Cited by 574 · see citing works
Self-citationNeuronal activity regulates extracellular tau in vivo
Yamada, K., Holth, J. K., Liao, F., Stewart, F. R., Mahan, T. E., Jiang, H., Cirrito, J. R., Patel, T. K., Hochgräfe, K., Mandelkow, E., et al. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20131685 · Cited by 574 · see citing works
Self-citationRoh, J. H., Huang, Y., Bero, A. W., Kasten, T., Stewart, F. R., Bateman, R. J., & Holtzman, D. M. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004291 · Cited by 563 · see citing works
Self-citationMachado, R. B., Hipólide, D. C., Benedito‐Silva, A. A., & Tufik, S. (2004) · Brain Research · doi:10.1016/j.brainres.2004.01.019 · Cited by 424 · see citing works
Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo
Busche, M. A., Wegmann, S., Dujardin, S., Commins, C., Schiantarelli, J., Klickstein, N., Kamath, T. V., Carlson, G. A., Nelken, I., & Hyman, B. T. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0289-8 · Cited by 413 · see citing works
Cirrito, J. R., May, P. C., O'Dell, M. A., Taylor, J. W., Parsadanian, M., Cramer, J. W., Audia, J. E., Nissen, J. S., Bales, K. R., Paul, S. M., et al. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-26-08844.2003 · Cited by 394 · see citing works
Self-citationEffect of sleep on overnight cerebrospinal fluid amyloid β kinetics
Lucey, B. P., Hicks, T. J., McLeland, J. S., Toedebusch, C. D., Boyd, J., Elbert, D. L., Patterson, B. W., Baty, J., Morris, J. C., Ovod, V., et al. (2018) · Annals of Neurology · doi:10.1002/ana.25117 · Cited by 362 · see citing works
Self-citationYamada, K., Cirrito, J. R., Stewart, F. R., Jiang, H., Finn, M. B., Holmes, B. B., Binder, L. I., Mandelkow, E.-M., Diamond, M. I., Lee, V. M.-Y., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.2569-11.2011 · Cited by 351 · see citing works
Self-citationHyperglycemia modulates extracellular amyloid-β concentrations and neuronal activity in vivo
Macauley, S. L., Stanley, M., Caesar, E. E., Yamada, S. A., Raichle, M. E., Perez, R., Mahan, T. E., Sutphen, C. L., & Holtzman, D. M. (2015) · Journal of Clinical Investigation · doi:10.1172/jci79742 · Cited by 211 · see citing works
Self-citationSupramammillary glutamate neurons are a key node of the arousal system
Pedersen, N. P., Ferrari, L., Venner, A., Wang, J. L., Abbott, S. B. G., Vujovic, N., Arrigoni, E., Saper, C. B., & Fuller, P. M. (2017) · Nature Communications · doi:10.1038/s41467-017-01004-6 · Cited by 203 · see citing works
Self-citationAge and amyloid effects on human central nervous system amyloid‐beta kinetics
Patterson, B. W., Elbert, D. L., Mawuenyega, K. G., Kasten, T., Ovod, V., Ma, S., Xiong, C., Chott, R., Yarasheski, K., Sigurdson, W., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24454 · Cited by 200 · see citing works
Self-citationTau Kinetics in Neurons and the Human Central Nervous System
Sato, C., Barthélemy, N. R., Mawuenyega, K. G., Patterson, B. W., Gordon, B. A., Jockel-Balsarotti, J., Sullivan, M., Crisp, M. J., Kasten, T., Kirmess, K. M., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.04.035 · Cited by 154 · see citing works
Extracellular α-synuclein levels are regulated by neuronal activity
Yamada, K., & Iwatsubo, T. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0241-0 · Cited by 148 · see citing works
Chronic Sleep Disruption Advances the Temporal Progression of Tauopathy in P301S Mutant Mice
Zhu, Y., Zhan, G., Fenik, P., Brandes, M., Bell, P., François, N., Shulman, K., & Veasey, S. C. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.0275-18.2018 · Cited by 106 · see citing works
Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy
Yanamandra, K., Patel, T. K., Jiang, H., Schindler, S., Ulrich, J. D., Boxer, A. L., Miller, B. L., Kerwin, D. R., Gallardo, G., Stewart, F., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aal2029 · Cited by 100 · see citing works
Self-citationAnalysis of in vivo turnover of tau in a mouse model of tauopathy
Yamada, K., Patel, T. K., Hochgräfe, K., Mahan, T. E., Jiang, H., Stewart, F. R., Mandelkow, E., & Holtzman, D. M. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0052-5 · Cited by 76 · see citing works
Self-citationLactate production and neurotransmitters; evidence from microdialysis studies
Uehara, T., Sumiyoshi, T., Itoh, H., & Kurata, K. (2008) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2008.04.001 · Cited by 39 · see citing works
Flagged first, then by citations
1 of the 33 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204 · see citing works
Self-citationCoupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep
Fultz, N. E., Bonmassar, G., Setsompop, K., Stickgold, R. A., Rosen, B. R., Polimeni, J. R., & Lewis, L. D. (2019) · Science · doi:10.1126/science.aax5440 · Cited by 1,197 · see citing works
Glymphatic failure as a final common pathway to dementia
Nedergaard, M., & Goldman, S. A. (2020) · Science · doi:10.1126/science.abb8739 · Cited by 1,145 · see citing works
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994 · see citing works
Cerebral amyloid angiopathy and Alzheimer disease — one peptide, two pathways
Greenberg, S. M., Bacskai, B. J., Hernandez-Guillamon, M., Pruzin, J., Sperling, R., & van Veluw, S. J. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-019-0281-2 · Cited by 947 · see citing works
Perivascular spaces in the brain: anatomy, physiology and pathology
Wardlaw, J. M., Benveniste, H., Nedergaard, M., Zlokovic, B. V., Mestre, H., Lee, H., Doubal, F. N., Brown, R., Ramirez, J., MacIntosh, B. J., et al. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0312-z · Cited by 870 · see citing works
Protein transmission in neurodegenerative disease
Peng, C., Trojanowski, J. Q., & Lee, V. M.-Y. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0333-7 · Cited by 625 · see citing works
Rasmussen, M. K., Mestre, H., & Nedergaard, M. (2021) · Physiological Reviews · doi:10.1152/physrev.00031.2020 · Cited by 622 · see citing works
The Brain’s Glymphatic System: Current Controversies
Mestre, H., Mori, Y., & Nedergaard, M. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.04.003 · Cited by 609 · see citing works
Wang, C., & Holtzman, D. M. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0478-5 · Cited by 589 · see citing works
Self-citationSleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut
Vaccaro, A., Kaplan Dor, Y., Nambara, K., Pollina, E. A., Lin, C., Greenberg, M. E., & Rogulja, D. (2020) · Cell · doi:10.1016/j.cell.2020.04.049 · Cited by 541 · see citing works
Genomics of circadian rhythms in health and disease
Rijo‐Ferreira, F., & Takahashi, J. S. (2019) · Genome Medicine · doi:10.1186/s13073-019-0704-0 · Cited by 537 · see citing works
Association between sleep duration and cognitive decline
Ma, Y., Liang, L., Zheng, F., Shi, L., Zhong, B., & Xie, W. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.13573 · Cited by 535 · see citing works
The different autophagy degradation pathways and neurodegeneration
Fleming, A., Bourdenx, M., Fujimaki, M., Karabiyik, C., Krause, G. J., Lopez, A., Martín‐Segura, A., Puri, C., Scrivo, A., Skidmore, J., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.01.017 · Cited by 485 · see citing works
Alzheimer’s disease: insights into pathology, molecular mechanisms, and therapy
Zheng, Q., & Wang, X. (2024) · Protein & Cell · doi:10.1093/procel/pwae026 · Cited by 454 · see citing works
Pathogenesis, diagnostics, and therapeutics for Alzheimer's disease: Breaking the memory barrier
Tryphena, K. P., Shukla, R., Khatri, D. K., & Vora, L. K. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102481 · Cited by 418 · see citing works
Bubu, O. M., Andrade, A. G., Umasabor-Bubu, O. Q., Hogan, M. M., Turner, A. D., de Leon, M. J., Ogedegbe, G., Ayappa, I., Jean-Louis G, G., Jackson, M. L., et al. (2020) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2019.101250 · Cited by 389 · see citing works
Sleep deprivation impairs molecular clearance from the human brain
Eide, P. K., Vinje, V., Pripp, A. H., Mardal, K., & Ringstad, G. A. (2020) · Brain · doi:10.1093/brain/awaa443 · Cited by 387 · see citing works
Sleep disorders and cancer: State of the art and future perspectives
Mogavero, M. P., DelRosso, L. M., Fanfulla, F., Bruni, O., & Ferri, R. (2020) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2020.101409 · Cited by 326 · see citing works
Microglia, Lifestyle Stress, and Neurodegeneration
Madore, C., Yin, Z., Leibowitz, J. A., & Butovsky, O. (2020) · Immunity · doi:10.1016/j.immuni.2019.12.003 · Cited by 310 · see citing works
Sleep deprivation and its association with diseases- a review
Liew, S. C., & Aung, T. (2020) · Sleep Medicine · doi:10.1016/j.sleep.2020.07.048 · Cited by 318 · see citing works
Mechanisms of secretion and spreading of pathological tau protein
Brunello, C. A., Merezhko, M., Uronen, R.-L., & Huttunen, H. J. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03349-1 · Cited by 304 · see citing works
Sleep deprivation and stress: a reciprocal relationship
Nollet, M., Wisden, W., & Franks, N. P. (2020) · Interface Focus · doi:10.1098/rsfs.2019.0092 · Cited by 307 · see citing works
Glymphatic system clears extracellular tau and protects from tau aggregation and neurodegeneration
Ishida, K., Yamada, K., Nishiyama, R., Hashimoto, T., Nishida, I., Abe, Y., Yasui, M., & Iwatsubo, T. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20211275 · Cited by 291 · see citing works
Tau: Enabler of diverse brain disorders and target of rapidly evolving therapeutic strategies
Chang, C.-W., Shao, E., & Mucke, L. (2021) · Science · doi:10.1126/science.abb8255 · Cited by 263 · see citing works
Sleep as a Potential Biomarker of Tau and β-Amyloid Burden in the Human Brain
Winer, J. R., Mander, B. A., Helfrich, R. F., Maaß, A., Harrison, T. M., Baker, S. L., Knight, R. T., Jagust, W. J., & Walker, M. P. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.0503-19.2019 · Cited by 259 · see citing works
Circadian rhythms in neurodegenerative disorders
Nassan, M. M., & Videnović, A. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00577-7 · Cited by 259 · see citing works
Modifiable Risk Factors for Alzheimer’s Disease
Edwards III, G. A., Gamez, N., Escobedo Jr., G., Calderon, O., & Moreno-Gonzalez, I. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00146 · Cited by 253 · see citing works
Cellular and pathological functions of tau
Bravo, C. P., Naguib, S. A., & Gan, L. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00753-9 · Cited by 245 · see citing works
An ocular glymphatic clearance system removes β-amyloid from the rodent eye
Wang, X., Lou, N., Eberhardt, A., Yang, Y., Kusk, P., Xu, Q., Förstera, B., Peng, S., Shi, M., Ladrón-de-Guevara, A., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aaw3210 · Cited by 239 · see citing works
New approaches to symptomatic treatments for Alzheimer’s disease
Cummings, J. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00424-9 · Cited by 226 · see citing works
Rösler, T. W., Marvian, A. T., Brendel, M., Nykänen, N.-P., Höllerhage, M., Schwarz, S. C., Hopfner, F., Koeglsperger, T., Respondek, G., Schweyer, K., et al. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.101644 · Cited by 219 · see citing works
Glucose metabolic crosstalk and regulation in brain function and diseases
Zhang, S., Lachance, B. B., Mattson, M. P., & Jia, X. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2021.102089 · Cited by 205 · see citing works
Regulation of the Blood–Brain Barrier by Circadian Rhythms and Sleep
Cuddapah, V. A., Zhang, S., & Sehgal, A. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.05.001 · Cited by 201 · see citing works
Relationship Between Amyloid-β Deposition and Blood–Brain Barrier Dysfunction in Alzheimer’s Disease
Wang, D., Chen, F., Han, Z., Yin, Z., Ge, X., & Lei, P. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.695479 · Cited by 201 · see citing works
Herring, W. J., Ceesay, P., Snyder, E., Bliwise, D. L., Budd, K., Hutzelmann, J., Stevens, J., Lines, C., & Michelson, D. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12035 · Cited by 202 · see citing works
Gao, C., Chapagain, N. Y., & Scullin, M. K. (2019) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.9891 · Cited by 194 · see citing works
Systemic factors as mediators of brain homeostasis, ageing and neurodegeneration
Pluvinage, J. V., & Wyss-Coray, T. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0255-9 · Cited by 191 · see citing works
Plascencia‐Villa, G., & Perry, G. L. (2020) · Antioxidants and Redox Signaling · doi:10.1089/ars.2020.8134 · Cited by 188 · see citing works
Li, Y., Sahakian, B. J., Kang, J., Langley, C., Zhang, W., Xie, C., Xiang, S., Yu, J., Cheng, W., & Feng, J. (2022) · Nature Aging · doi:10.1038/s43587-022-00210-2 · Cited by 183 · see citing works
Reactive astrocytes: The nexus of pathological and clinical hallmarks of Alzheimer’s disease
Price, B. R., Johnson, L. A., & Norris, C. M. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101335 · Cited by 173 · see citing works
The Role of Glymphatic System in Alzheimer’s and Parkinson’s Disease Pathogenesis
Buccellato, F. R., D’Anca, M., Serpente, M., Arighi, A., & Galimberti, D. (2022) · Biomedicines · doi:10.3390/biomedicines10092261 · Cited by 184 · see citing works
It's complicated: The relationship between sleep and Alzheimer's disease in humans
Lucey, B. P. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105031 · Cited by 165 · see citing works
Self-citationBrain clearance is reduced during sleep and anesthesia
Miao, A., Luo, T., Hsieh, B., Edge, C. J., Gridley, M., Wong, R. T. C., Constandinou, T. G., Wisden, W., & Franks, N. P. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01638-y · Cited by 170 · see citing works
Profound degeneration of wake‐promoting neurons in Alzheimer's disease
Oh, J. Y., Eser, R. A., Ehrenberg, A. J., Morales, D. O., Petersen, C., Kudlacek, J., Dunlop, S. R., Theofilas, P., Resende, E. D. P. F., Cosme, C. G., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.06.3916 · Cited by 146 · see citing works
Cell-to-Cell Transmission of Tau and α-Synuclein
Uemura, N., Uemura, M. T., Luk, K. C., Lee, V. M. ‐., & Trojanowski, J. Q. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.03.012 · Cited by 141 · see citing works
Lananna, B. V., & Musiek, E. S. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104832 · Cited by 145 · see citing works
Sleep Disturbance as Potential Risk and Progression Factor for Parkinson’s Disease
Bohnen, N. I., & Hu, M. T. M. (2019) · Journal of Parkinson s Disease · doi:10.3233/jpd-191627 · Cited by 144 · see citing works
Niu, L., Zhang, F., Xu, X., Yang, Y., Li, S., Liu, H., & Le, W. (2021) · Brain Pathology · doi:10.1111/bpa.13028 · Cited by 149 · see citing works
Emerging links between cerebrovascular and neurodegenerative diseases—a special role for pericytes
Lendahl, U., Nilsson, P., & Betsholtz, C. (2019) · EMBO Reports · doi:10.15252/embr.201948070 · Cited by 141 · see citing works
Leng, Y., BLACKWELL, T. L., Cawthon, P. M., Ancoli‐Israel, S., Stone, K. L., & Yaffe, K. S. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2020.1623 · Cited by 142 · see citing works
Egroo, M. V., Koshmanova, E., Vandewalle, G., & Jacobs, H. I. L. (2022) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2022.101592 · Cited by 132 · see citing works
Parhizkar, S., Gent, G., Chen, Y., Rensing, N. R., Gratuze, M., Strout, G. W., Sviben, S., Tycksen, E., Zhang, Q., Erdmann-Gilmore, P., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.ade6285 · Cited by 134 · see citing works
Self-citationSleep Deprivation Affects Tau Phosphorylation in Human Cerebrospinal Fluid
Barthélemy, N. R., Liu, H., Lu, W., Kotzbauer, P. T., Bateman, R. J., & Lucey, B. P. (2020) · Annals of Neurology · doi:10.1002/ana.25702 · Cited by 128 · see citing works
Self-citationThe interconnected causes and consequences of sleep in the brain
Lewis, L. D. (2021) · Science · doi:10.1126/science.abi8375 · Cited by 130 · see citing works
Xu, Y., Du, S., Marsh, J. A., Horie, K., Sato, C., Ballabio, A., Karch, C. M. M., Holtzman, D. M., & Zheng, H. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0738-0 · Cited by 121 · see citing works
Self-citationSleep Architecture, Obstructive Sleep Apnea, and Cognitive Function in Adults
Pase, M. P., Harrison, S. L., Misialek, J. R., Kline, C. E., Cavuoto, M. G., Baril, A., Yiallourou, S. R., Bisson, A., Himali, D., Leng, Y., et al. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.25152 · Cited by 127 · see citing works
Sleep Disturbance as a Potential Modifiable Risk Factor for Alzheimer’s Disease
Minakawa, E. N., Wada, K., & Nagai, Y. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20040803 · Cited by 118 · see citing works
The role of innate immunity in Alzheimer's disease
Ennerfelt, H. E., & Lukens, J. R. (2020) · Immunological Reviews · doi:10.1111/imr.12896 · Cited by 121 · see citing works
Microglia regulate sleep through calcium-dependent modulation of norepinephrine transmission
Ma, C., Li, B., Silverman, D., Ding, X., Li, A., Xiao, C., Huang, G., Worden, K., Muroy, S. E., Chen, W., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-023-01548-5 · Cited by 122 · see citing works
The Interstitial System of the Brain in Health and Disease
Shetty, A. K., & Zanirati, G. (2020) · Aging and Disease · doi:10.14336/ad.2020.0103 · Cited by 114 · see citing works
Meningeal Lymphatics: From Anatomy to Central Nervous System Immune Surveillance
Papadopoulos, Z., Herz, J., & Kipnis, J. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1900838 · Cited by 108 · see citing works
Study, F. T. A., Grau‐Rivera, O., Operto, G., Falcón, C., Sánchez‐Benavides, G., Cacciaglia, R., Brugulat‐Serrat, A., Gramunt, N., Salvadó, G., Suárez‐Calvet, M., et al. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-019-0547-3 · Cited by 109 · see citing works
Han, F., Brown, G. L., Zhu, Y., Belkin-Rosen, A., Lewis, M. M., Du, G., Gu, Y., Eslinger, P. J., Mailman, R. B., Huang, X., et al. (2021) · Movement Disorders · doi:10.1002/mds.28643 · Cited by 110 · see citing works
The effect of insomnia on development of Alzheimer’s disease
Sadeghmousavi, S., Eskian, M., Rahmani, F., & Rezaei, N. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01960-9 · Cited by 113 · see citing works
Sleep and risk of parkinsonism and Parkinson’s disease: a population-based study
Lysen, T. S., Darweesh, S. K. L., Ikram, M. K., Luik, A. I., & Ikram, M. A. (2019) · Brain · doi:10.1093/brain/awz113 · Cited by 105 · see citing works
Neural consequences of chronic sleep disruption
Zamore, Z. H., & Veasey, S. C. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.05.007 · Cited by 105 · see citing works
Suvorexant Acutely Decreases Tau Phosphorylation and Aβ in the Human CNS
Lucey, B. P., Liu, H., Toedebusch, C. D., Freund, D., Redrick, T., Chahin, S. L., Mawuenyega, K. G., Bollinger, J. G., Ovod, V., Barthélemy, N. R., et al. (2023) · Annals of Neurology · doi:10.1002/ana.26641 · Cited by 106 · see citing works
Self-citationZhao, N., Chen, Q.-G., Chen, X., Liu, X.-T., Geng, F., Zhu, M.-M., Yan, F.-L., Zhang, Z.-J., & Ren, Q.-G. (2023) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2022.11.013 · Cited by 105 · see citing works
The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment
Lv, T., Zhao, B., Hu, Q., & Zhang, X. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.689098 · Cited by 105 · see citing works
Salehpour, F., Khademi, M., Евгеньевич, Б. Д., & DiDuro, J. O. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23062975 · Cited by 103 · see citing works
Alzheimer's disease pathophysiology in the Retina
Gaire, B. P., Koronyo, Y., Fuchs, D.-T. S., Shi, H., Rentsendorj, A., Danziger, R., Vit, J., Mirzaei, N., Doustar, J., Sheyn, J., et al. (2024) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2024.101273 · Cited by 102 · see citing works
Circadian Rhythm Sleep–Wake Disorders in Older Adults
Kim, J. H., Elkhadem, A. R., & Duffy, J. F. (2022) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2022.02.003 · Cited by 106 · see citing works
Effects of acute sleep loss on diurnal plasma dynamics of CNS health biomarkers in young men
Benedict, C., Blennow, K., Zetterberg, H., & Cedernaes, J. (2020) · Neurology · doi:10.1212/wnl.0000000000008866 · Cited by 100 · see citing works
Association Between Slow-Wave Sleep Loss and Incident Dementia
Himali, J. J., Baril, A., Cavuoto, M. G., Yiallourou, S. R., Wiedner, C. D., Himali, D., DeCarli, C. S., Redline, S. S., Beiser, A., Seshadri, S. S., et al. (2023) · JAMA Neurology · doi:10.1001/jamaneurol.2023.3889 · Cited by 100 · see citing works
Slow‐wave sleep and motor progression in Parkinson disease
Schreiner, S. J., Imbach, L., Werth, E., Poryazova, R., Baumann‐Vogel, H., Valko, P. O., Murer, T., Noaín, D., & Baumann, C. R. (2019) · Annals of Neurology · doi:10.1002/ana.25459 · Cited by 97 · see citing works
Li, G., Cao, Y., Tang, X., Huang, J., Cai, L., & Zhou, L. (2022) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x221098145 · Cited by 99 · see citing works
Current Status of Clinical Trials on Tau Immunotherapies
Ji, C., & Sigurdsson, E. M. (2021) · Drugs · doi:10.1007/s40265-021-01546-6 · Cited by 96 · see citing works
Local Sleep and Alzheimer’s Disease Pathophysiology
Mander, B. A. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.525970 · Cited by 97 · see citing works
Reid, M. J., Beltran-Lobo, P., Johnson, L., Perez‐Nievas, B. G., & Noble, W. J. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.572850 · Cited by 92 · see citing works
Kamondi, A., Grigg-Damberger, M. M., Löscher, W., Tanila, H., & Horvath, A. A. (2024) · Nature Reviews Neurology · doi:10.1038/s41582-024-00932-4 · Cited by 102 · see citing works
Xu, W., Tan, L., Su, B., Yu, H., Bi, Y., Yue, X., Dong, Q., & Yu, J. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12117 · Cited by 91 · see citing works
Tau immunotherapies: Lessons learned, current status and future considerations
Sandusky-Beltran, L. A., & Sigurdsson, E. M. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108104 · Cited by 90 · see citing works
Defining circadian disruption in neurodegenerative disorders
Colwell, C. S. (2021) · Journal of Clinical Investigation · doi:10.1172/jci148288 · Cited by 90 · see citing works
Eide, P. K., Pripp, A. H., Berge, B., Hrubos‐Strøm, H., Ringstad, G. A., & Valnes, L. M. (2022) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x221090747 · Cited by 91 · see citing works
Impact of sleep disturbances on neurodegeneration: Insight from studies in animal models
Owen, J. E., & Veasey, S. C. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104820 · Cited by 90 · see citing works
Glymphatic dysfunction in isolated REM sleep behavior disorder
Lee, D. A., Lee, H., & Park, K. M. (2021) · Acta Neurologica Scandinavica · doi:10.1111/ane.13573 · Cited by 88 · see citing works
Alzheimer’s disease – the journey of a healthy brain into organ failure
Golde, T. E. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00523-1 · Cited by 90 · see citing works
Peng, F., Lü, J., Su, K., Liu, X., Luo, H., He, B., Wang, C., Zhang, X., An, F., Lv, D., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.04.018 · Cited by 88 · see citing works
Self-citationGlymphatic dysfunction in Alzheimer’s disease: A critical appraisal
Keil, S. A., Jansson, D., Braun, M., & Iliff, J. J. (2025) · Science · doi:10.1126/science.adv8269 · Cited by 96 · see citing works
Imaging the effect of the circadian light–dark cycle on the glymphatic system in awake rats
Cai, X., Qiao, J., Kulkarni, P. P., Harding, I. C., Ebong, E. E., & Ferris, C. F. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1914017117 · Cited by 86 · see citing works
EEG alterations during wake and sleep in mild cognitive impairment and Alzheimer's disease
D’Atri, A., Scarpelli, S., Gorgoni, M., Truglia, I., Lauri, G., Cordone, S., Ferrara, M., Marra, C., Rossini, P. M., & Gennaro, L. D. (2021) · iScience · doi:10.1016/j.isci.2021.102386 · Cited by 92 · see citing works
Morawska, M. M., Moreira, C. G., Ginde, V. R., Valko, P. O., Weiß, T., Büchele, F., Imbach, L., Masneuf, S., Kollarik, S., Prymaczok, N. C., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abe7099 · Cited by 83 · see citing works
Acute sleep loss decreases CSF‐to‐blood clearance of Alzheimer's disease biomarkers
Liu, H., Barthélemy, N. R., Ovod, V., Bollinger, J. G., He, Y., Chahin, S. L., Androff, B., Bateman, R. J., & Lucey, B. P. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.12930 · Cited by 86 · see citing works
Self-citationConsequences of Metabolic Disruption in Alzheimer's Disease Pathology
Ryu, J. C., Zimmer, E. R., Rosa‐Neto, P., & Yoon, S. O. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00755-y · Cited by 84 · see citing works
Actigraphy‐estimated sleep and 24‐hour activity rhythms and the risk of dementia
Lysen, T. S., Luik, A. I., Ikram, M. K., Tiemeier, H. W., & Ikram, M. K. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12122 · Cited by 83 · see citing works
Achieving brain clearance and preventing neurodegenerative diseases—A glymphatic perspective
Kylkilahti, T. M., Berends, E., Ramos, M., Shanbhag, N. C., Töger, J., Bloch, K. M., & Lundgaard, I. (2021) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20982388 · Cited by 89 · see citing works
Alzheimer’s disease: Neurotransmitters of the sleep-wake cycle
Erum, J. V., Dam, D. V., & Deyn, P. P. D. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.07.019 · Cited by 81 · see citing works
Jurcău, M. C., Jurcău, A., Cristian, A., Hogea, V. O., Diaconu, R. G., & Nunkoo, V. S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910535 · Cited by 90 · see citing works
Feld, G. B., & Jan Born, A. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0490-9 · Cited by 79 · see citing works
- Authors
- Holth, J. K., Fritschi, S. K., Wang, C., Pedersen, N. P., Cirrito, J. R., Mahan, T. E., Finn, M. B., Manis, M., Geerling, J. C., Fuller, P. M., Lucey, B. P., & Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- Emory University (US)
- University of Iowa Hospitals and Clinics (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Holth, Jerrah K.
- Fritschi, Sarah K.
- Holtzman, David M.
- ORCID
- Venue
- Science
- Published
- 2019-02-22
- Volume
- 363
- Issue
- 6429
- Pages
- 880-884
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC6410369
- OpenAlex
- W2912003143
- Cited by
- 813
- References
- 33
- Citations by year
- 2026: 117 · 2025: 121 · 2024: 128 · 2023: 115 · 2022: 98 · 2021: 98 · 2020: 87 · 2019: 49
- FWCI
- 56.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute on Aging (AG047999, AG054863, AG05681, AG26276)
- National Institute of Neurological Disorders and Stroke (NS074969, NS073613, K08NS105929, NS089381)
- National Center for Advancing Translational Sciences (TR000448, TR000450)
- BrightFocus Foundation (A2017114F)
- Deutsche Forschungsgemeinschaft (3625/1-1)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- sleep-wake cycle, tau protein, cerebrospinal fluid, interstitial fluid, chronic sleep deprivation, Alzheimer's disease, amyloid-beta, tau pathology
- MeSH terms
- Animals, Brain, Circadian Rhythm, Female, Male, Mice, Transgenic, Sleep, Sleep Deprivation, Wakefulness, Amyloid beta-Peptides, tau Proteins, Extracellular Fluid, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
