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Clearance systems in the brain—implications for Alzheimer disease
Open accessAbstract
Accumulation of toxic protein aggregates-amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles-is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood-brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ.
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“The concomitant BBB dysfunction not only reduces the intracerebral transport of glucose and other nutrients,[ 10 ] but also decreases the removal of excess metabolites,[ 11 ] thus alters the homeostasis in the central nervous system (CNS).”
From Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit (2021) · cites this paper as [11]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“The major reason for the accumulation of RAP‐RL along the cerebral microvasculature lies in that a key component of the nanostructure, RAP, a peptide derived from RAGE's nature ligand S100P, can specifically bind to RAGE overexpressing on the endothelium of AD cerebral vasculature.[ 15 , 38 ]”
From Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit (2021) · cites this paper as [15]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Moreover, the expression of AQP4 on astrocytic endfeet decrease and their perivascular polarization is inhibited, ultimately leading to lymphatic clearance dysfunction.[ 11 , 43 ]”
From Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit (2021) · cites this paper as [11]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Due to the lack of appropriate model systems, the role of LRP1 at the BBB and the overall relevance of BBB clearance are insufficiently understood and debated (4,7).”
From Endothelial LRP1 transports amyloid-β1–42 across the blood-brain barrier (2015) · cites this paper as [4]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In a healthy brain, Ab homeostasis is maintained by a balance between its production and clearance, whereas in AD brain overproduction and/or reduced clearance of Ab result in the formation of amyloid deposits (4).”
From Differential protective effects of connective tissue growth factor against Aβ neurotoxicity on neurons and glia (2017) · cites this paper as [4]
Experimental — accuracy not yet measured
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In the citing paper
“Glial cells such as astrocytes and microglia also play a role in Aβ42 clearance by several mechanisms including proteolytic degradation of endocytosed proteins, clearance through the blood brain barrier, and clearance from to the CSF via the glymphatic pathway [46].”
From The Sigma-2 Receptor/TMEM97, PGRMC1, and LDL Receptor Complex Are Responsible for the Cellular Uptake of Aβ42 and Its Protein Aggregates (2020) · cites this paper as [46]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
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“An important clearance pathway for cerebral Aβ is the steady transport across the blood–brain barrier (BBB) [11].”
From PCSK9 acts as a key regulator of Aβ clearance across the blood–brain barrier (2022) · cites this paper as [11]
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“Low Aβ levels within the healthy brain are maintained through degradation, elimination via interstitial fluid (ISF) bulk flow, cerebrospinal fluid (CSF) absorption into the circulatory and lymphatic system, or transport across the blood-brain barrier (BBB) (3,4).”
From Endothelial LRP1 transports amyloid-β1–42 across the blood-brain barrier (2015) · cites this paper as [4]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“RAP, a peptide derived from RAGE's nature ligand, S100B, can bind RAGE effectively.[ 15 ]”
From Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit (2021) · cites this paper as [15]
Experimental — accuracy not yet measuredIn the citing paper
“AQP4 levels are reduced in CAA; since AQP4 plays a vital role in glymphatic Aβ clearance in AD brain parenchyma, this consequently impairs Aβ clearance [606, 608].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [606]
In the citing paper
“AQP4 levels are reduced in CAA; since AQP4 plays a vital role in glymphatic Aβ clearance in AD brain parenchyma, this consequently impairs Aβ clearance [606, 608].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [606]
In the citing paper
“It has been suggested that vascular damage associated with CAA disrupts vascular drainage and homeostasis in the CNS, thereby impairing Aβ clearance and aggravating AD pathogenesis [606].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [606]
In the citing paper
“In contrast, Aβ peptides in the CNS can also move into the circulatory system, where the peptides are phagocytosed by the monocytes or neutrophils, directly degraded by the enzymes, or further transported to the peripheral organs or tissues for degradation or excretion.”
From Amyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future (2023) · cites this paper as [28]
In the citing paper
“We and others have shown that both neurons and glia can clear extracellular Ab through endocytosis for subsequent lysosomal degradation or secretion of amyloiddegrading enzymes for extracellular clearance (4,7).”
From Differential protective effects of connective tissue growth factor against Aβ neurotoxicity on neurons and glia (2017) · cites this paper as [4]
In the citing paper
“Impairment of Ab uptake and clearance by neurons, glia, and blood-brain-barrier endothelial cells may explain why the level of Ab is elevated and accumulates during AD progression (4).”
From Differential protective effects of connective tissue growth factor against Aβ neurotoxicity on neurons and glia (2017) · cites this paper as [4]
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Citations
Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Sperling, R. A., Aisen, P. S., Beckett, L. A., Bennett, D. A., Craft, S., Fagan, A. M., Iwatsubo, T., Jack, C. R., Kaye, J., Montine, T. J., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.003 · Cited by 7,155
Iliff, J. J., Wang, M., Liao, Y., Plogg, B. A., Peng, W., Gundersen, G. A., Benveniste, H., Vates, G. E., Deane, R., Goldman, S. A., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003748 · Cited by 5,824
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
Self-citationStructure and function of the blood–brain barrier
Abbott, N. J., Patabendige, A. A. K., Dolman, D. E. M., Yusof, S. R., & Begley, D. J. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.07.030 · Cited by 5,185
2016 Alzheimer's disease facts and figures
Alzheimer's Association (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.03.001 · Cited by 5,069
Querfurth, H. W., & LaFerla, F. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0909142 · Cited by 4,569
Structural and functional features of central nervous system lymphatic vessels
Louveau, A., Smirnov, I., Keyes, T. J., Eccles, J. D., Rouhani, S. J., Peske, J. D., Derecki, N. C., Castle, D., Mandell, J. W., Lee, K. S., et al. (2015) · Nature · doi:10.1038/nature14432 · Cited by 4,413
Jack, C. R., Knopman, D. S., Jagust, W. J., Petersen, R. C., Weiner, M. W., Aisen, P. S., Shaw, L. M., Vemuri, P., Wiste, H. J., Weigand, S. D., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70291-0 · Cited by 4,396
Meta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer’s Disease
(EADI), E. A. D. I., Lambert, J.-C., (GERAD), G. A. E. R. I. A. D., Alzheimer's Disease Genetic Consortium (ADGC), (CHARGE), C. F. H. A. A. R. I. G. E., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C., et al. (2013) · Nature Genetics · doi:10.1038/ng.2802 · Cited by 4,336
Hearing loss and cognitive decline in older adults
Lin, F. R., Yaffe, K., Xia, J., Xue, Q.-L., Harris, T. B., Purchase-Helzner, E., Satterfield, S., Ayonayon, H. N., Ferrucci, L., Simonsick, E. M., et al. (2013) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2013.1868 · Cited by 4,017
Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.263 · Cited by 3,459
2013 Alzheimer's disease facts and figures
Thies, W. H., & Bleiler, L. (2013) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2013.02.003 · Cited by 3,372
Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326
Blennow, K., de Leon, M. J., & Zetterberg, H. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69113-7 · Cited by 3,134
Self-citationNeurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders
Zlokovic, B. V. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3114 · Cited by 2,969
The projected effect of risk factor reduction on Alzheimer's disease prevalence
Barnes, D. E., & Yaffe, K. S. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70072-2 · Cited by 2,846
Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity
DeKosky, S. T., & Scheff, S. W. (1990) · Annals of Neurology · doi:10.1002/ana.410270502 · Cited by 2,376
Alzheimer Disease in the US Population: Prevalence Estimates Using the 2000 Census
Hebert, L. E., Scherr, P. A., Bienias, J. L., Bennett, D. A., & Evans, D. A. (2003) · Archives of Neurology · doi:10.1001/archneur.60.8.1119 · Cited by 2,168
The clinical use of structural MRI in Alzheimer disease
Frisoni, G. B., Fox, N. C., Jack, C. R., Scheltens, P., & Thompson, P. M. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.215 · Cited by 2,113
Decreased Clearance of CNS β-Amyloid in Alzheimer’s Disease
Mawuenyega, K. G., Sigurdson, W., Ovod, V., Munsell, L., Kasten, T., Morris, J. C., Yarasheski, K. E., & Bateman, R. J. (2010) · Science · doi:10.1126/science.1197623 · Cited by 2,078
The glymphatic system: a beginner's guide
Jessen, N. A., Munk, A. S. F., Lundgaard, I., & Nedergaard, M. (2015) · Neurochemical Research · doi:10.1007/s11064-015-1581-6 · Cited by 2,075
Jarrett, J. T., Berger, E. P., & Lansbury, P. T. (1993) · Biochemistry · doi:10.1021/bi00069a001 · Cited by 2,022
3D structure of Alzheimer's amyloid-β(1–42) fibrils
Lührs, T., Ritter, C., Adrian, M., Riek-Loher, D., Bohrmann, B., Döbeli, H., Schubert, D. A., & Riek, R. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506723102 · Cited by 2,001
Cerebrospinal fluid and plasma biomarkers in Alzheimer disease
Blennow, K., Hampel, H., Weiner, M., & Zetterberg, H. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.4 · Cited by 1,863
Self-citationEpidemiology of Alzheimer disease
Reitz, C., Brayne, C., & Mayeux, R. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.2 · Cited by 1,675
Impairment of paravascular clearance pathways in the aging brain
Kress, B. T., Iliff, J. J., Xia, M., Wang, M., Wei, H. S., Zeppenfeld, D., Xie, L., Kang, H., Xu, Q., Liew, J. A., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24271 · Cited by 1,521
Diffusion in Brain Extracellular Space
Syková, E., & Nicholson, C. (2008) · Physiological Reviews · doi:10.1152/physrev.00027.2007 · Cited by 1,481
Self-citationShibata, M., Yamada, S., Kumar, S. R., Calero, M., Bading, J., Frangione, B., Holtzman, D. M., Miller, C. A., Strickland, D. K., Ghiso, J., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10498 · Cited by 1,413
Self-citationNeural mechanisms of ageing and cognitive decline
Bishop, N. A., Lu, T., & Yankner, B. A. (2010) · Nature · doi:10.1038/nature08983 · Cited by 1,323
Cerebral Arterial Pulsation Drives Paravascular CSF–Interstitial Fluid Exchange in the Murine Brain
Iliff, J. J., Wang, M., Zeppenfeld, D. M., Venkataraman, A., Plog, B. A., Liao, Y., Deane, R., & Nedergaard, M. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.1592-13.2013 · Cited by 1,319
Apolipoprotein E controls cerebrovascular integrity via cyclophilin A
Bell, R. D., Winkler, E. A., Singh, I., Sagare, A. P., Deane, R., Wu, Z., Holtzman, D. M., Betsholtz, C., Armulik, A., Sallstrom, J., et al. (2012) · Nature · doi:10.1038/nature11087 · Cited by 1,293
Alzheimer disease: Epidemiology, diagnostic criteria, risk factors and biomarkers
Reitz, C., & Mayeux, R. P. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.12.024 · Cited by 1,271
Converging concepts of protein folding in vitro and in vivo
Hartl, F. U., & Hayer-Hartl, M. K. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1591 · Cited by 1,235
The Intersection of Amyloid Beta and Tau at Synapses in Alzheimer’s Disease
Spires-Jones, T. L., & Hyman, B. T. (2014) · Neuron · doi:10.1016/j.neuron.2014.05.004 · Cited by 1,201
Impairment of Glymphatic Pathway Function Promotes Tau Pathology after Traumatic Brain Injury
Iliff, J. J., Chen, M. J., Plog, B. A., Zeppenfeld, D. M., Soltero, M., Yang, L., Singh, I., Deane, R., & Nedergaard, M. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3020-14.2014 · Cited by 1,159
Brain-wide pathway for waste clearance captured by contrast-enhanced MRI
Iliff, J. J., Lee, H., Yu, M., Feng, T., Logan, J., Nedergaard, M., & Benveniste, H. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67677 · Cited by 1,148
2012 Alzheimer's disease facts and figures Alzheimer's Association ∗
Thies, W. H., & Bleiler, L. (2012) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2012.02.001 · Cited by 1,014
Sleep and Alzheimer disease pathology--a bidirectional relationship
Ju, Y.-E. S., Lucey, B. P., & Holtzman, D. M. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.269 · Cited by 996
Metabolic Regulation of Brain Aβ by Neprilysin
Iwata, N., Tsubuki, S., Takaki, Y., Shirotani, K., Lu, B., Gerard, N. P., Gerard, C. J., Hama, E., Lee, H.-J., & Saido, T. C. (2001) · Science · doi:10.1126/science.1059946 · Cited by 982
Central nervous system pericytes in health and disease
Winkler, E. A., Bell, R. D., & Zlokovic, B. V. (2011) · Nature Neuroscience · doi:10.1038/nn.2946 · Cited by 962
Self-citationOxidative stress in Alzheimer’s disease
Smith, M. A., Rottkamp, C. A., Nunomura, A., Raina, A. K., & Perry, G. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(00)00040-5 · Cited by 895
Mathiisen, T. M., Lehre, K. P., Danbolt, N. C., & Ottersen, O. (2010) · Glia · doi:10.1002/glia.20990 · Cited by 893
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
Multiplicity of cerebrospinal fluid functions: new challenges in health and disease
Johanson, C. E., Duncan, J. A., Klinge, P. M., Brinker, T., Stopa, E. G., & Silverberg, G. D. (2008) · Cerebrospinal Fluid Research · doi:10.1186/1743-8454-5-10 · Cited by 861
LRP/Amyloid β-Peptide Interaction Mediates Differential Brain Efflux of Aβ Isoforms
Deane, R., Wu, Z., Sagare, A., Davis, J., Du Yan, S., Hamm, K., Xu, F., Parisi, M., LaRue, B., Hu, H. W., et al. (2004) · Neuron · doi:10.1016/j.neuron.2004.07.017 · Cited by 828
Self-citationInsulin-degrading Enzyme Regulates Extracellular Levels of Amyloid β-Protein by Degradation
Qiu, W. Q., Walsh, D. M., Ye, Z., Vekrellis, K., Zhang, J., Podlisny, M. B., Rosner, M. R., Safavi, A., Hersh, L. B., & Selkoe, D. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.49.32730 · Cited by 812
The Genetics of Alzheimer's Disease
Bertram, L., & Tanzi, R. E. (2012) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-385883-2.00008-4 · Cited by 794
Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology
Abbott, N. J. (2004) · Neurochemistry International · doi:10.1016/j.neuint.2003.11.006 · Cited by 786
Rennels, M. L., Gregory, T. F., Blaumanis, O. R., Fujimoto, K., & Grady, P. A. (1985) · Brain Research · doi:10.1016/0006-8993(85)91383-6 · Cited by 752
Sleep Quality and Preclinical Alzheimer Disease
Ju, Y.-E. S., McLeland, J. S., Toedebusch, C. D., Xiong, C., Fagan, A. M., Duntley, S. P., Morris, J. C., & Holtzman, D. M. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.2334 · Cited by 744
Miyata, M., & Smith, J. D. (1996) · Nature Genetics · doi:10.1038/ng0996-55 · Cited by 735
Nedergaard, M. (2013) · Science · doi:10.1126/science.1240514 · Cited by 718
The role of microglia in amyloid clearance from the AD brain
Lee, C. Y. D., & Landreth, G. E. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0433-4 · Cited by 701
Weller, R. O., Subash, M., Preston, S., Mazanti, I., & Carare, R. O. (2008) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00133.x · Cited by 697
Self-citationAn overview of APP processing enzymes and products.
Chow, V. W., Mattson, M. P., Wong, P. C., & Gleichmann, M. (2010) · NeuroMolecular Medicine · doi:10.1007/s12017-009-8104-z · Cited by 684
Weller, R. O., Massey, A., Newman, T. A., Hutchings, M., Kuo, Y.-M., & Roher, A. E. (1998) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65616-7 · Cited by 679
Immune activation in brain aging and neurodegeneration: too much or too little?
Lucin, K. M., & Wyss-Coray, T. (2009) · Neuron · doi:10.1016/j.neuron.2009.08.039 · Cited by 679
Carare, R. O., Bernardes‐Silva, M., Newman, T. A., Page, A. M., Nicoll, J. A. R., Perry, V. H., & Weller, R. O. (2008) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00926.x · Cited by 665
Self-citationThe blood-brain barrier: an engineering perspective
Wong, A. D., Ye, M., Levy, A. F., Rothstein, J. D., Bergles, D. E., & Searson, P. C. (2013) · Frontiers in Neuroengineering · doi:10.3389/fneng.2013.00007 · Cited by 662
Mechanisms of fluid movement into, through and out of the brain: evaluation of the evidence
Hladky, S. B., & Barrand, M. A. (2014) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-11-26 · Cited by 633
Deane, R., Singh, I., Sagare, A. P., Bell, R. D., Ross, N. T., LaRue, B., Love, R., Perry, S., Paquette, N., Deane, R. J., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci58642 · Cited by 619
Self-citationApoE and Aβ in Alzheimer’s Disease: Accidental Encounters or Partners?
Kanekiyo, T., Xu, H., & Bu, G. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.045 · Cited by 608
Neuronal 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 606
ApoE genotype accounts for the vast majority of AD risk and AD pathology
Raber, J., Huang, Y., & Ashford, J. W. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.12.023 · Cited by 599
Human amyloid-β synthesis and clearance rates as measured in cerebrospinal fluid in vivo
Bateman, R. J., Munsell, L. Y., Morris, J. C., Swarm, R., Yarasheski, K. E., & Holtzman, D. M. (2006) · Nature Medicine · doi:10.1038/nm1438 · Cited by 599
Blood–Brain Barrier Dysfunction as a Cause and Consequence of Alzheimer's Disease
Erickson, M. A., & Banks, W. A. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.135 · Cited by 572
Self-reported sleep and β-amyloid deposition in community-dwelling older adults
Spira, A. P., Gamaldo, A. A., An, Y., Wu, M. N., Simonsick, E. M., Bilgel, M., Zhou, Y., Wong, D. F., Ferrucci, L., & Resnick, S. M. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.4258 · Cited by 570
Verghese, P. B., Castellano, J. M., Garai, K., Wang, Y., Jiang, H., Shah, A., Bu, G., Frieden, C., & Holtzman, D. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220484110 · Cited by 556
Reiman, E. M., Quiroz, Y. T., Fleisher, A. S., Chen, K., Velez-Pardo, C., Jimenez-Del-Rio, M., Fagan, A. M., Shah, A. R., Alvarez, S., Arbelaez, A., et al. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70228-4 · Cited by 541
Oxidative Stress and Autophagy
Kiffin, R., Bandyopadhyay, U., & Cuervo, A. M. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.152 · Cited by 529
Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system.
Plog, B. A., Dashnaw, M. L., Hitomi, E., Peng, W., Liao, Y., Lou, N., Deane, R., & Nedergaard, M. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.3742-14.2015 · Cited by 525
Neurobiology of Mental Illness
(2011) · Oxford University Press eBooks · doi:10.1093/med/9780199798261.001.0001 · Cited by 523
Physiology of the choroid plexus.
Cserr, H. F. (1971) · Physiological Reviews · doi:10.1152/physrev.1971.51.2.273 · Cited by 514
Alzheimer disease therapy—moving from amyloid-β to tau
Giacobini, E., & Gold, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.223 · Cited by 501
Tau imaging: early progress and future directions
Villemagne, V. L., Fodero-Tavoletti, M. T., Masters, C. L., & Rowe, C. C. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70252-2 · Cited by 501
Antiamyloidogenic and Neuroprotective Functions of Cathepsin B: Implications for Alzheimer's Disease
Mueller-Steiner, S., Zhou, Y., Arai, H., Roberson, E. D., Sun, B., Chen, J., Wang, X., Yu, G.-Q., Esposito, L., Mucke, L., et al. (2006) · Neuron · doi:10.1016/j.neuron.2006.07.027 · Cited by 482
Alzheimer’s Disease Genetics: From the Bench to the Clinic
Karch, C. M., Cruchaga, C., & Goate, A. M. (2014) · Neuron · doi:10.1016/j.neuron.2014.05.041 · Cited by 473
Deciphering the mechanism underlying late-onset Alzheimer disease
Krstic, D., & Knuesel, I. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.236 · Cited by 457
Tau, tangles, and Alzheimer's disease
Binder, L. I., Guillozet-Bongaarts, A. L., García‐Sierra, F., & Berry, R. W. (2004) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.08.014 · Cited by 450
Bacskai, B. J., Kajdasz, S. T., Christie, R. H., Carter, C., Games, D., Seubert, P. A., Schenk, D., & Hyman, B. T. (2001) · Nature Medicine · doi:10.1038/85525 · Cited by 445
Silverberg, G. D., Mayo, M. R., Saul, T., Rubenstein, E., & McGuire, D. (2003) · The Lancet Neurology · doi:10.1016/s1474-4422(03)00487-3 · Cited by 433
Astrocytes accumulate Aβ42 and give rise to astrocytic amyloid plaques in Alzheimer disease brains
Nagele, R. G., D’Andrea, M. R., Lee, H., Venkataraman, V., & Wang, H.-Y. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02361-8 · Cited by 416
Hawkes, C. A., & McLaurin, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805453106 · Cited by 397
Autophagy in microglia degrades extracellular β-amyloid fibrils and regulates the NLRP3 inflammasome
Cho, M.-H., Cho, K., Kang, H.-J., Jeon, E.-Y., Kim, H.-S., Kwon, H.-J., Kim, H.-M., Kim, D.-H., & Yoon, S.-Y. (2014) · Autophagy · doi:10.4161/auto.29647 · Cited by 395
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
Miners, J. S., Baig, S., Palmer, J. C., Palmer, L. E., Kehoe, P. G., & Love, S. (2008) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00132.x · Cited by 393
Matrix Metalloproteinases Expressed by Astrocytes Mediate Extracellular Amyloid-β Peptide Catabolism
Yin, K.-J., Cirrito, J. R., Yan, P., Hu, X., Xiao, Q., Pan, X., Bateman, R., Song, H., Hsu, F.-F., Turk, J., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2085-06.2006 · Cited by 381
Is There a Cerebral Lymphatic System?
Iliff, J. J., & Nedergaard, M. (2013) · Stroke · doi:10.1161/strokeaha.112.678698 · Cited by 377
Cerebral amyloid angiopathy and its relationship to Alzheimer’s disease
Thal, D. R., Griffin, W. S. T., de Vos, R. A. I., & Ghebremedhin, E. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0366-2 · Cited by 372
The function and structure of the cerebrospinal fluid outflow system
Pollay, M. (2010) · Cerebrospinal Fluid Research · doi:10.1186/1743-8454-7-9 · Cited by 371
Hawkes, C. A., Härtig, W., Kacza, J., Schliebs, R., Weller, R. O., Nicoll, J. A. R., & Carare, R. O. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0801-7 · Cited by 365
Self-citationDrainage of interstitial fluid from different regions of rat brain
Szentistvanyi, I., Patlak, C. S., Ellis, R. A., & Cserr, H. F. (1984) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1984.246.6.f835 · Cited by 355
Orešković, D., & Klarica, M. (2010) · Brain Research Reviews · doi:10.1016/j.brainresrev.2010.04.006 · Cited by 349
Degradation of the Alzheimer's Amyloid β Peptide by Endothelin-converting Enzyme*
Eckman, E., Reed, D. K., & Eckman, C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007579200 · Cited by 345
Reduced hippocampal metabolism in MCI and AD
Mosconi, L., Tsui, W. H., Santi, S. D., Li, J., Rusinek, H., Convit, A. J., Li, Y., Boppana, M., & de Leon, M. J. (2005) · Neurology · doi:10.1212/01.wnl.0000163856.13524.08 · Cited by 335
Self-citationDrainage of cerebral interstitial fluid into deep cervical lymph of the rabbit
Bradbury, M. W., Cserr, H. F., & Westrop, R. J. (1981) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1981.240.4.f329 · Cited by 335
Proteasomal degradation of tau protein
David, D. C., Layfield, R., Serpell, L., Narain, Y., Goedert, M., & Spillantini, M. G. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01137.x · Cited by 327
Efflux of radiolabeled polyethylene glycols and albumin from rat brain
Cserr, H. F., Cooper, D. N., Suri, P. K., & Patlak, C. S. (1981) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1981.240.4.f319 · Cited by 323
The radiologic prediction of Alzheimer disease: the atrophic hippocampal formation.
de Leon, M. J., Golomb, J. B., GEORGE, A. E., Convit, A. J., Tarshish, C. Y., McRae, T., Santi, S. D., Smith, G. S., Ferris, S. H., & Noz, M. E. (1993) · PubMed Central · Cited by 322
Ren, Z., Iliff, J. J., Yang, L., Yang, J., Chen, X., Chen, M. J., Giese, R. N., Wang, B., Shi, X., & Nedergaard, M. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.30 · Cited by 317
Yang, L., Kress, B. T., Weber, H. J., Thiyagarajan, M., Wang, B., Deane, R., Benveniste, H., Iliff, J. J., & Nedergaard, M. (2013) · Journal of Translational Medicine · doi:10.1186/1479-5876-11-107 · Cited by 317
Mechanisms to explain the reverse perivascular transport of solutes out of the brain
Schley, D., Carare-Nnadi, R., Please, C. P., Perry, V. H., & Weller, R. O. (2006) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2005.07.005 · Cited by 293
Blood–brain-barriers in aging and in Alzheimer’s disease
Marques, F., Sousa, J. C., Sousa, N., & Palha, J. A. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-38 · Cited by 285
Wu, Y., & Swaab, D. F. (2007) · Sleep Medicine · doi:10.1016/j.sleep.2006.11.010 · Cited by 284
Dawkins, E., & Small, D. H. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12675 · Cited by 279
Castillo-Carranza, D. L., Sengupta, U., Guerrero-Muñoz, M. J., Lasagna-Reeves, C. A., Gerson, J. E., Singh, G., Estes, D. M., Barrett, A. D. T., Dineley, K. T., Jackson, G. R., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3192-13.2014 · Cited by 278
Interstitial fluid drainage is impaired in ischemic stroke and Alzheimer’s disease mouse models
Arbel‐Ornath, M., Hudry, E., Eikermann‐Haerter, K., Hou, S. S., Gregory, J. L., Zhao, L., Betensky, R. A., Frosch, M. P., Greenberg, S. M., & Bacskai, B. J. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1145-2 · Cited by 265
Autosomal Recessive Causes Likely in Early-Onset Alzheimer Disease
Wingo, T. S. (2012) · Archives of Neurology · doi:10.1001/archneurol.2011.221 · Cited by 265
Zlokovic, B. V., Deane, R., Sagare, A. P., Bell, R. D., & Winkler, E. A. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07002.x · Cited by 261
Evidence for impaired amyloid β clearance in Alzheimer's disease
Wildsmith, K. R., Holley, M., Savage, J. C., Skerrett, R., & Landreth, G. E. (2013) · Alzheimer s Research & Therapy · doi:10.1186/alzrt187 · Cited by 249
Preston, S., Steart, P. V., Wilkinson, A., Nicoll, J. A. R., & Weller, R. O. (2003) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.2003.00424.x · Cited by 245
Increased in Vivo Amyloid-β42 Production, Exchange, and Loss in Presenilin Mutation Carriers
Potter, R., Patterson, B. W., Elbert, D. L., Ovod, V., Kasten, T., Sigurdson, W., Mawuenyega, K., Blazey, T., Goate, A., Chott, R., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005615 · Cited by 236
Drowning stars: reassessing the role of astrocytes in brain edema
Thrane, A. S., Thrane, V. R., & Nedergaard, M. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.08.010 · Cited by 227
Yasojima, K., McGeer, E. G., & McGeer, P. L. (2001) · Brain Research · doi:10.1016/s0006-8993(01)03008-6 · Cited by 224
Lysosomal system pathways: Genes to neurodegeneration in Alzheimer's disease
Nixon, R. A., & Cataldo, A. M. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9s331 · Cited by 222
Intracellular Mechanisms of Amyloid Accumulation and Pathogenesis in Alzheimer's Disease
Glabe, C. (2001) · Journal of Molecular Neuroscience · doi:10.1385/jmn:17:2:137 · Cited by 222
Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease.
Chesser, A. S., Pritchard, S. M., & Johnson, G. V. W. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00122 · Cited by 219
Blennow, K., Bogdanović, N., Alafuzoff, I. I., Ekman, R., & Davidsson, P. (1996) · Journal of Neural Transmission · doi:10.1007/bf01273157 · Cited by 217
Self-citationMendelsohn, A. R., & Larrick, J. W. (2013) · Rejuvenation Research · doi:10.1089/rej.2013.1530 · Cited by 216
Early detection of Alzheimer's disease using PiB and FDG PET
Cohen, A. D., & Klunk, W. E. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.05.001 · Cited by 216
Di Marco, L. Y., Marzo, A., Muñoz-Ruiz, M., Ikram, M. A., Kivipelto, M., Ruefenacht, D., Venneri, A., Soininen, H., Wanke, I., Ventikos, Y. A., et al. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-132225 · Cited by 215
Bradbury, M. W. B., & Westrop, R. J. (1983) · The Journal of Physiology · doi:10.1113/jphysiol.1983.sp014731 · Cited by 211
Mechanisms of Amyloid-β Peptide Clearance: Potential Therapeutic Targets for Alzheimer's Disease
Yoon, S.-S., & AhnJo, S.-M. (2012) · Biomolecules and Therapeutics · doi:10.4062/biomolther.2012.20.3.245 · Cited by 205
Wilcock, D. M., Munireddy, S. K., Rosenthal, A., Ugen, K. E., Gordon, M. N., & Morgan, D. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2003.09.015 · Cited by 202
Phosphorylation by cAMP-dependent protein kinase inhibits the degradation of tau by calpain.
Litersky, J. M., & Johnson, G. V. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45982-0 · Cited by 201
Plasma Aβ in Alzheimer's disease—up or down?
Zetterberg, H., & Blennow, K. (2006) · The Lancet Neurology · doi:10.1016/s1474-4422(06)70503-8 · Cited by 200
Self-citationPositron Emission Tomography in the Study of Aging and Senile Dementia
Ferris, S. H., de Leon, M. J., Wolf, A. P., Farkas, T., Christman, D. R., Reisberg, ., Fowler, J. S., MacGregor, R. R., Goldman, A. G., GEORGE, A. E., et al. (1980) · Neurobiology of Aging · doi:10.1016/0197-4580(80)90005-6 · Cited by 198
Clearance of amyloid β-peptide from brain: transport or metabolism?
Zlokovic, B. V., Yamada, S., Holtzman, D., Ghiso, J., & Frangione, B. (2000) · Nature Medicine · doi:10.1038/77397 · Cited by 186
Self-citationHawkes, C. A., Sullivan, P. M., Hands, S. L., Weller, R. O., Nicoll, J. A. R., & Carare, R. O. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041636 · Cited by 182
Self-citationFailure of Perivascular Drainage of β‐amyloid in Cerebral Amyloid Angiopathy
Hawkes, C. A., Jayakody, N., Johnston, D. A., Bechmann, I., & Carare, R. O. (2014) · Brain Pathology · doi:10.1111/bpa.12159 · Cited by 170
Self-citationGrimm, M. O. W., Mett, J., Stahlmann, C. P., Haupenthal, V. J., Zimmer, V. C., & Hartmann, T. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00098 · Cited by 170
Are amyloid-degrading enzymes viable therapeutic targets in Alzheimer’s disease?
Nalivaeva, N. N., Beckett, C., Belyaev, N. D., & Turner, A. J. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07510.x · Cited by 169
Panzenboeck, U., Balazs, Z., Sovic, A., Hrzenjak, A., Levak-Frank, S., Wintersperger, A., Malle, E., & Sattler, W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207601200 · Cited by 169
Genetics of Alzheimer's Disease
Guerreiro, R. J., & Hardy, J. (2014) · Neurotherapeutics · doi:10.1007/s13311-014-0295-9 · Cited by 168
The role of extracellular Tau in the spreading of neurofibrillary pathology
Medina, M., & Avila, J. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00113 · Cited by 161
Water Exchange of Central Nervous System and Cerebrospinal Fluid
Bering, E. A. (1952) · Journal of neurosurgery · doi:10.3171/jns.1952.9.3.0275 · Cited by 158
Hawkes, C. A., Gatherer, M., Sharp, M. M., Dorr, A. E., Yuen, H. M., Kalaria, R. N., Weller, R. O., & Carare, R. O. (2013) · Aging Cell · doi:10.1111/acel.12045 · Cited by 157
Self-citationLin, T.-W., Shih, Y.-H., Chen, S.-J., Lien, C.-H., Chang, C.-Y., Huang, T.-Y., Chen, S.-H., Jen, C. J., & Kuo, Y.-M. (2015) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2014.12.005 · Cited by 153
Neurovascular Defects and Faulty Amyloid-β Vascular Clearance in Alzheimer's Disease
Sagare, A. P., Bell, R. D., & Zloković, B. V. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-129037 · Cited by 152
The lysosome and neurodegenerative diseases
Zhang, L., Sheng, R., & Qin, Z. (2009) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmp031 · Cited by 152
Braak, H., Zetterberg, H., Tredici, K. D., & Blennow, K. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1139-0 · Cited by 148
Self-citationStoodley, M. A., Brown, S. A., Brown, C. J., & Jones, N. R. (1997) · Journal of neurosurgery · doi:10.3171/jns.1997.86.4.0686 · Cited by 145
Amyloid-beta transporter expression at the blood-CSF barrier is age-dependent
Pascale, C. L., Miller, M. C., Chiu, C., Boylan, M. R., Caralopoulos, I. N., González, L., Johanson, C. E., & Silverberg, G. D. (2011) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-8-21 · Cited by 140
Genetic markers for diagnosis and pathogenesis of Alzheimer's disease
Kim, D., Yeo, S. H., Park, J.-M., Choi, J. Y., Lee, T.-H., Park, S. Y., Ock, M. S., Eo, J., Kim, H., & Cha, H. (2014) · Gene · doi:10.1016/j.gene.2014.05.031 · Cited by 133
Zloković, B. V. (1995) · Pharmaceutical Research · doi:10.1023/a:1016254514167 · Cited by 131
Oxidized neprilysin in aging and Alzheimer’s disease brains
Wang, D.-S., Iwata, N., Hama, E., Saido, T. C., & Dickson, D. W. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.09.003 · Cited by 131
Morris, A. W. J., Carare, R. O., Schreiber, S., & Hawkes, C. A. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00251 · Cited by 131
Self-citation[18F]THK-5117 PET for assessing neurofibrillary pathology in Alzheimer’s disease
Harada, R., Okamura, N., Furumoto, S., Furukawa, K., Ishiki, A., Tomita, N., Hiraoka, K., Watanuki, S., Shidahara, M., Miyake, M., et al. (2015) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-015-3035-4 · Cited by 128
Circadian clock disruption in neurodegenerative diseases: cause and effect?
Musiek, E. S. (2015) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00029 · Cited by 125
Sérot, J., Zmudka, J., & Jouanny, P. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-111964 · Cited by 123
Telomere Shortening and Alzheimer’s Disease
Cai, Z., Yan, L., & Ratka, A. (2012) · NeuroMolecular Medicine · doi:10.1007/s12017-012-8207-9 · Cited by 121
Fitz, N. F., Cronican, A. A., Saleem, M., Fauq, A. H., Chapman, R., Lefterov, I., & Koldamova, R. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.1937-12.2012 · Cited by 119
Transport of Leucine‐Enkephalin Across the Blood‐Brain Barrier in the Perfused Guinea Pig Brain
Zloković, B. V., Lipovac, M. N., Begley, D. J., Davson, H., & Rakić, L. (1987) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1987.tb03431.x · Cited by 118
The role of intracellular amyloid β in Alzheimer's disease
Li, M. C., Chen, L., Lee, D. H. S., Yu, L., & Zhang, Y. (2007) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.08.002 · Cited by 118
ElAli, A., & Rivest, S. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00045 · Cited by 115
Zlokovic, B. V., Begley, D. J., & Chain-Eliash, D. G. (1985) · Brain Research · doi:10.1016/0006-8993(85)90423-8 · Cited by 114
Self-citationWheel-running in a transgenic mouse model of Alzheimer's disease: Protection or symptom?
Richter, H., Ambrée, O., Lewejohann, L., Herring, A., Keyvani, K., Paulus, W., Palme, R., Touma, C., Schäbitz, W., & Sachser, N. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.02.005 · Cited by 107
Water influx into cerebrospinal fluid is primarily controlled by aquaporin-4, not by aquaporin-1
Igarashi, H., Tsujita, M., Kwee, I. L., & Nakada, T. (2013) · Neuroreport · doi:10.1097/wnr.0000000000000042 · Cited by 104
Balasubramanian, A. B., Kawas, C. H., Peltz, C. B., Brookmeyer, R., & Corrada, M. M. (2012) · Neurology · doi:10.1212/wnl.0b013e318266fc77 · Cited by 102
Shea, T. B., & Beermann, M. L. (1994) · Molecular Biology of the Cell · doi:10.1091/mbc.5.8.863 · Cited by 101
The adaptive immune system in diseases of the central nervous system
Wraith, D. C., & Nicholson, L. B. (2012) · Journal of Clinical Investigation · doi:10.1172/jci58648 · Cited by 101
Ito, S., Ohtsuki, S., & Terasaki, T. (2006) · Neuroscience Research · doi:10.1016/j.neures.2006.07.006 · Cited by 99
Aging, Amyloid, and Alzheimer's Disease: A Perspective in Honor of Carl Cotman
Selkoe, D. J. (2003) · Neurochemical Research · doi:10.1023/a:1026065122854 · Cited by 98
Characteristics and consequences of muscarinic receptor activation by tau protein
Gómez‐Ramos, A., Dı́az-Hernández, M., Rubio, A., Díaz‐Hernandéz, J. I., Miras‐Portugal, M. T., & Ávila, J. (2009) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2009.04.006 · Cited by 95
The Abluminal Endothelial Membrane in Neurovascular Remodeling in Health and Disease
Hermann, D. M., & ElAli, A. (2012) · Science Signaling · doi:10.1126/scisignal.2002886 · Cited by 86
Ito, S., Ohtsuki, S., Kamiie, J., Nezu, Y., & Terasaki, T. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04938.x · Cited by 85
Aquaporin-4 mediates astrocyte response to β-amyloid
Yang, W., Wu, Q., Chan, Y., Gao, J., Xiao, M., Gu, M., Ding, J., & Hu, G. (2012) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2012.02.002 · Cited by 84
Alzheimer’s and ABC transporters — new opportunities for diagnostics and treatment
Pahnke, J., Langer, O., & Krohn, M. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.04.001 · Cited by 84
Apolipoprotein E: Essential Catalyst of the Alzheimer Amyloid Cascade
Potter, H., & Wısnıewskı, T. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/489428 · Cited by 84
Pathology of clinical and preclinical Alzheimer’s disease
Thal, D. R., Arnim, C. A. F. V., Griffin, W. S. T., Yamaguchi, H., Mrak, R. E., Attems, J., & Upadhaya, A. R. (2013) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-013-0449-5 · Cited by 80
Neurobiology of Mental Illness
Dünner, D. L. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.9.1530-a · Cited by 77
Elevated cerebrospinal fluid pressure in patients with Alzheimer's disease
Silverberg, G. D., Mayo, M. R., Saul, T., FELLMANN, J. D., & McGuire, D. (2006) · Cerebrospinal Fluid Research · doi:10.1186/1743-8454-3-7 · Cited by 76
Environmental Enrichment Counteracts Alzheimer’s Neurovascular Dysfunction in TgCRND8 Mice
Herring, A., Yasin, H., Ambrée, O., Sachser, N., Paulus, W., & Keyvani, K. (2007) · Brain Pathology · doi:10.1111/j.1750-3639.2007.00094.x · Cited by 75
Bulk flow of cerebrospinal fluid into brain in response to acute hyperosmolality
Pullen, R. G. L., Depasquale, M. J., & Cserr, H. F. (1987) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1987.253.3.f538 · Cited by 75
Navari, R. M., Wei, E. P., Kontos, H. A., & Patterson, J. L. (1978) · Microvascular Research · doi:10.1016/0026-2862(78)90064-x · Cited by 74
Intracellular distribution of amyloid beta peptide and its relationship to the lysosomal system
Zheng, L. P., Cedazo-Mı́nguez, Á., Hallbeck, M., Jerhammar, F., Marcusson, J. O., & Terman, A. (2012) · Translational Neurodegeneration · doi:10.1186/2047-9158-1-19 · Cited by 73
O’Donnell, J., Ding, F., & Nedergaard, M. (2015) · Current Sleep Medicine Reports · doi:10.1007/s40675-014-0004-6 · Cited by 72
Aβ immunotherapy for Alzheimer’s disease: effects on apoE and cerebral vasculopathy
Sakai, K., Boche, D., Carare, R., Johnston, D., Holmes, C., Love, S., & Nicoll, J. A. R. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1340-9 · Cited by 72
Self-citationProtein filtration and secretion at human body fluid barriers
Felgenhauer, K. (1980) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00589509 · Cited by 71
The innate immune system in Alzheimer's disease
Boutajangout, A., & Wisniewski, T. (2013) · International Journal of Cell Biology · doi:10.1155/2013/576383 · Cited by 69
Evidence for lymphatic Aβ clearance in Alzheimer's transgenic mice
Pappolla, M., Sambamurti, K., Vidal, R., Pacheco-Quinto, J., Poeggeler, B., & Matsubara, E. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.07.012 · Cited by 69
Lim, N. K.-H., Villemagne, V. L., Soon, C. P. W., Laughton, K. M., Rowe, C. C., McLean, C., Masters, C. L., Evin, G. M., & Li, Q. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-101974 · Cited by 67
Amyloid: Little proteins, big clues
Schnabel, J. (2011) · Nature · doi:10.1038/475s12a · Cited by 65
Astrocytes: a cellular player in Aβ clearance and degradation
Guénette, S. Y. (2003) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(03)00112-6 · Cited by 64
Fujiyoshi, M., Tachikawa, M., Ohtsuki, S., Ito, S., Uchida, Y., Akanuma, S., Kamiie, J., Hashimoto, T., Hosoya, K., Iwatsubo, T., et al. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07311.x · Cited by 63
The lymphatic system: A historical perspective
Loukas, M., Bellary, S. S., Kuklinski, M., et al. (2011) · Clinical Anatomy · doi:10.1002/ca.21194 · Cited by 59
Prenatal high‐fat diet alters the cerebrovasculature and clearance of β‐amyloid in adult offspring
Hawkes, C. A., Gentleman, S., Nicoll, J. A. R., & Carare, R. O. (2014) · The Journal of Pathology · doi:10.1002/path.4468 · Cited by 56
Self-citationPicchioni, D., Reith, R. M., Nadel, J., & Smith, C. B. (2014) · Brain Sciences · doi:10.3390/brainsci4010150 · Cited by 56
Carare, R. O., Teeling, J. L., Hawkes, C. A., Püntener, U., Weller, R. O., Nicoll, J. A. R., & Perry, V. H. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-48 · Cited by 51
Self-citationAkanuma, S.-I., Ohtsuki, S., Doi, Y., Tachikawa, M., Ito, S., Hori, S., Asashima, T., Hashimoto, T., Yamada, K., Ueda, K., et al. (2008) · Neurochemistry International · doi:10.1016/j.neuint.2007.12.002 · Cited by 50
THE EXCHANGE OF MATERIAL BETWEEN CEREBROSPINAL FLUID AND BRAIN
Fenstermacher, J. D., & Patlak, C. S. (1975) · Elsevier eBooks · doi:10.1016/b978-0-12-197450-3.50017-5 · Cited by 49
Ito, S., Ueno, T., Ohtsuki, S., & Terasaki, T. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06708.x · Cited by 48
The Changing Concepts of Amyloid
Picken, M. M. (2001) · Archives of Pathology & Laboratory Medicine · doi:10.5858/2001-125-0038-tccoa · Cited by 48
APP mutations in the Aβ coding region are associated with abundant cerebral deposition of Aβ38
Moro, M. L., Giaccone, G., Lombardi, R., Indaco, A., Uggetti, A., Morbin, M., Saccucci, S., Fede, G. D., Catania, M., Walsh, D. M., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-1061-x · Cited by 39
Kawamura, S., Schürer, L., Goetz, A., Kempski, O. S., Schmucker, B., & Baethmann, A. (1990) · PubMed · Cited by 39
Two-Photon Imaging of Microglia in the Mouse Cortex In Vivo
Nimmerjahn, A. (2012) · Cold Spring Harbor Protocols · doi:10.1101/pdb.prot069294 · Cited by 38
Sources of Extracellular Tau and its Signaling
Ávila, J., Simón, D., Díaz-Hernández, M., Pintor, J. J., & Hernández, F. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131832 · Cited by 36
Irazuzta, J. E., de Courten‐Myers, G., Zemlan, F. P., Bekkedal, M. Y. V., & Rossi, J. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02764-0 · Cited by 36
Research works printed but not linked: 2
- Hetzel, L. 65 Years and Over Population: 2000. Census 2000 Brief (DIANE Publishing, 2008).
- Milford, H. in Studies in Intracranial Physiology and Surgery 1st edn Ch. 1 (ed. Cushing, H.) 1–50 (Oxford University Press, 1926).
Cited by
Sorted by citations
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Leng, F., & Edison, P. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-020-00435-y · Cited by 3,179
Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders
Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.188 · Cited by 3,076
Self-citationThe Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease
Iadecola, C. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.030 · Cited by 2,480
Blood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,312
Self-citationThe Cellular Phase of Alzheimer’s Disease
De Strooper, B., & Karran, E. (2016) · Cell · doi:10.1016/j.cell.2015.12.056 · Cited by 1,990
Metadata
- Authors
- Tarasoff-Conway, J. M., Carare, R. O., Osorio, R. S., Glodzik, L., Butler, T., Fieremans, E., Axel, L., Rusinek, H., Nicholson, C., Zlokovic, B. V., Frangione, B., Blennow, K., Ménard, J., Zetterberg, H., Wisniewski, T., & de Leon, M. J.
- Affiliations
- New York University (US)
- Southampton General Hospital (GB)
- NYU Langone Health (US)
- University of Gothenburg (SE)
- Université Paris Descartes (FR)
- ORCID
- Venue
- Nature Reviews Neurology
- Published
- 2015-07-21
- Volume
- 11
- Issue
- 8
- Pages
- 457-470
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- PMC
- PMC4694579
- OpenAlex
- W1767010801
- Cited by
- 1,678
- References
- 216
- Citations by year
- 2026: 165 · 2025: 178 · 2024: 190 · 2023: 163 · 2022: 184 · 2021: 183 · 2020: 162 · 2019: 137 · 2018: 118 · 2017: 129 · 2016: 53 · 2015: 15
- FWCI
- 12.83
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-03-29)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institute on Aging (AG008051, AG022374, R01AG022374, AG20245, AG 12101, R01AG012101, P30AG008051, R01AG020245, R01AG013616, AG 13616)
- National Heart, Lung, and Blood Institute (HL118624, R01HL118624, HL111724, R01HL111724)
- National Institute of Neurological Disorders and Stroke (NS028642, R01NS028642)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid-beta clearance, glymphatic system, meningeal lymphatic vessels, blood-brain barrier, astrocytes, tau hyperphosphorylation, amyloid plaques, brain waste clearance
- MeSH terms
- Alzheimer Disease, Blood-Brain Barrier, Brain, Cerebrospinal Fluid Proteins, Humans, Lymphatic System, Risk Factors, Biomarkers, Amyloid beta-Peptides, tau Proteins, Extracellular Fluid, Proteolysis, Absorption, Physiological
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