The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Synaptic Activity Regulates Interstitial Fluid Amyloid-β Levels In Vivo
Open accessAbstract
Aggregation of the amyloid-beta (Abeta) peptide in the extracellular space of the brain is central to Alzheimer's disease pathogenesis. Abeta aggregation is concentration dependent and brain region specific. Utilizing in vivo microdialysis concurrently with field potential recordings, we demonstrate that Abeta levels in the brain interstitial fluid are dynamically and directly influenced by synaptic activity on a timescale of minutes to hours. Using an acute brain slice model, we show that the rapid effects of synaptic activity on Abeta levels are primarily related to synaptic vesicle exocytosis. These results suggest that synaptic activity may modulate a neurodegenerative disease process, in this case by influencing Abeta metabolism and ultimately region-specific Abeta deposition. The findings also have important implications for treatment development.
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In the citing paper
“The lower abundance of plaques in the white matter could further be explained by the evidence that most neuronal Aβ is secreted at presynaptic terminals, thus favouring plaque deposition in the grey matter [50,51].”
From Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease (2024) · cites this paper as [51]
In the citing paper
“Depolarization and subsequent synaptic transmission causes Aβ to be produced presynaptically and then secreted into the brain extracellular fluid or interstitial fluid (ISF) (4–6).”
From Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans (2011) · cites this paper as [5]
In the citing paper
“TTX dramatically reduces neuronal activity and ISF Aβ levels in vivo (5).”
From Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans (2011) · cites this paper as [5]
In the citing paper
“Synaptic activity is one key regulator of brain Aβ production.”
From Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans (2011) · cites this paper as [5]
In the citing paper
“Synaptic activity is known to regulate Aβ levels through a presynaptic mechanism that is dependent on APP endocytosis and cleavage (4, 5) and through neurotransmitter-activated second messenger signaling pathways that alter APP processing into Aβ (7, 11, 12, 31).”
From Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans (2011) · cites this paper as [5]
In the citing paper
“Proteins linked to neurodegenerative diseases, including β-amyloid (Aβ) (8), α-synuclein (9), and tau (10), are present in the interstitial space surrounding cells of the brain.”
From Sleep Drives Metabolite Clearance from the Adult Brain (2013) · cites this paper as [8]
In the citing paper
“Overall, we feel we can confidently state APP and Aβ homeostasis are exquisitely regulated processes, and bioenergetic metabolism regulates these processes.”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [181]
In the citing paper
“Although the aggregates have been considered to be toxic, soluble Aβ at physiological levels have been identified to have biological functions, including enhancement of long-term potentiation (LTP),355–358 stimulation of neuronal differentiation,359 improvement of the brain’s ability to recover from injuries,360–363 inhibition of oxidative stress,364 antimicrobial activity365 and tumor suppression”
From Amyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future (2023) · cites this paper as [355]
In the citing paper
“Extracellular occurrence of oligomers is consistent with the rapid outpouring of Aβ, and perhaps small oligomers, into brain interstitial fluid, measured by microdialysis in mouse models and humans (Cirrito et al., 2005; Kang et al., 2007; Kang et al., 2009).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Cirrito et al., 2005
In the citing paper
“Synaptic activity has been shown to increase the secretion of Aβ in hippocampal slices and living rodent brain [26, 85].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [26]
Citations
Cites
A default mode of brain function
Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., & Shulman, G. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.2.676 · Cited by 12,190
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063
Searching for a baseline: Functional imaging and the resting human brain
Gusnard, D. A., & Raichle, M. E. (2001) · Nature Reviews Neuroscience · doi:10.1038/35094500 · Cited by 3,371
Buckner, R. L., Snyder, A. Z., Shannon, B. J., LaRossa, G., Sachs, R., Fotenos, A. F., Sheline, Y. I., Klunk, W. E., Mathis, C. A., Morris, J. C., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2177-05.2005 · Cited by 2,140
APP Processing and Synaptic Function
Kamenetz, F., Tomita, T., Hsieh, H., Seabrook, G., Borchelt, D., Iwatsubo, T., Sisodia, S., & Malinow, R. (2003) · Neuron · doi:10.1016/s0896-6273(03)00124-7 · Cited by 1,644
GSK-3α regulates production of Alzheimer's disease amyloid-β peptides
Phiel, C. J., Wilson, C., Lee, V. M. ‐., & Klein, P. S. (2003) · Nature · doi:10.1038/nature01640 · Cited by 1,211
Kawarabayashi, T., Younkin, L. H., Saido, T. C., Shoji, M., Ashe, K. H., & Younkin, S. G. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-02-00372.2001 · Cited by 1,053 · cited 1×
“Data represent mean 6 SEM. in humans, results in early onset, familial AD and develop Ab deposition in amyloid plaques beginning at about 8–9 months of age (Kawarabayashi et al., 2001).”
BackgroundEnvironmental Enrichment Reduces Aβ Levels and Amyloid Deposition in Transgenic Mice
Lazarov, O., Robinson, J., Tang, Y.-P., Hairston, I. S., Korade-Mirnics, Z., Lee, V. M.-Y., Hersh, L. B., Sapolsky, R. M., Mirnics, K., & Sisodia, S. S. (2005) · Cell · doi:10.1016/j.cell.2005.01.015 · Cited by 885
Regulation of Neurotransmitter Release by Metabotropic Glutamate Receptors
Cartmell, J., & Schoepp, D. D. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0750889.x · Cited by 883
Self-citationEvidence that production and release of amyloid beta-protein involves the endocytic pathway
Koo, E. H., & Squazzo, S. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32449-3 · Cited by 829
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Buckner, R. L., Andrews‐Hanna, J. R., & Schacter, D. L. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1440.011 · Cited by 9,761
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
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744
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
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
Self-citationBuckner, R. L., Sepulcre, J., Talukdar, T., Krienen, F. M., Liu, H., Hedden, T., Andrews-Hanna, J. R., Sperling, R. A., & Johnson, K. A. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5062-08.2009 · Cited by 2,862
Knopman, D. S., Amieva, H., Petersen, R. C., Chételat, G., Holtzman, D. M., Hyman, B. T., Nixon, R. A., & Jones, D. T. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00269-y · Cited by 2,606
Self-citationAmyloid-β–induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks
Palop, J. J., & Mucke, L. (2010) · Nature Neuroscience · doi:10.1038/nn.2583 · Cited by 1,651
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
Self-citationAlzheimer’s Disease: The Challenge of the Second Century
Holtzman, D. M., Morris, J. C., & Goate, A. M. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002369 · Cited by 1,424
Self-citationTrafficking and Proteolytic Processing of APP
Haass, C., Kaether, C., Thinakaran, G., & Sisodia, S. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006270 · Cited by 1,075
Sperling, R. A., LaViolette, P. S., O'Keefe, K., O'Brien, J., Rentz, D. M., Pihlajamaki, M., Marshall, G., Hyman, B. T., Selkoe, D. J., Hedden, T., et al. (2009) · Neuron · doi:10.1016/j.neuron.2009.07.003 · Cited by 1,027
AMPAR Removal Underlies Aβ-Induced Synaptic Depression and Dendritic Spine Loss
Hsieh, H., Boehm, J., Sato, C., Iwatsubo, T., Tomita, T., Sisodia, S., & Malinow, R. (2006) · Neuron · doi:10.1016/j.neuron.2006.10.035 · Cited by 1,042
Sleep disturbances increase the risk of dementia: a systematic review and meta-analysis
Shi, L., Chen, S.-J., Ma, M.-Y., Bao, Y.-P., Han, Y., Wang, Y.-M., Shi, J., Vitiello, M. V., & Lu, L. (2018) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2017.06.010 · Cited by 1,009
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
Self-citationNetwork abnormalities and interneuron dysfunction in Alzheimer disease
Palop, J. J., & Mucke, L. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.141 · Cited by 1,022
Neurotoxicity of Amyloid -Protein: Synaptic and Network Dysfunction
Mucke, L., & Selkoe, D. J. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006338 · Cited by 1,000
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Di Paolo, G., & Kim, T.-W. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3012 · Cited by 972
Amyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future
Zhang, Y., Chen, H., Li, R., Sterling, K., & Song, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01484-7 · Cited by 988
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
Self-citationA human brain vascular atlas reveals diverse mediators of Alzheimer’s risk
Yang, A. C., Vest, R. T., Kern, F., Lee, D. P., Agam, M., Maat, C. A., Losada, P. M., Chen, M. B., Schaum, N., Khoury, N., et al. (2022) · Nature · doi:10.1038/s41586-021-04369-3 · Cited by 797
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Martorell, A. J., Paulson, A. L., Suk, H.-J., Abdurrob, F., Drummond, G. T., Guan, W., Young, J. Z., Kim, D. N.-W., Kritskiy, O., Barker, S. J., et al. (2019) · Cell · doi:10.1016/j.cell.2019.02.014 · Cited by 798
The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.010 · Cited by 786
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Puzzo, D., Privitera, L., Leznik, E., Fà, M., Staniszewski, A., Palmeri, A., & Arancio, O. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2692-08.2008 · Cited by 740
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
Self-citationThe Evolution of Preclinical Alzheimer’s Disease: Implications for Prevention Trials
Sperling, R., Mormino, E., & Johnson, K. (2014) · Neuron · doi:10.1016/j.neuron.2014.10.038 · Cited by 725
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Perrin, R. J., Fagan, A. M., & Holtzman, D. M. (2009) · Nature · doi:10.1038/nature08538 · Cited by 702
Self-citationThe 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
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Cirrito, J. R., Kang, J.-E., Lee, J., Stewart, F. R., Verges, D. K., Silverio, L. M., Bu, G., Mennerick, S., & Holtzman, D. M. (2008) · Neuron · doi:10.1016/j.neuron.2008.02.003 · Cited by 635
Self-citationMemory loss in Alzheimer's disease
Jahn, H. (2013) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2013.15.4/hjahn · Cited by 653
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Kozai, T. D. Y., Jaquins-Gerstl, A. S., Vazquez, A. L., Michael, A. C., & Cui, X. T. (2015) · ACS Chemical Neuroscience · doi:10.1021/cn500256e · Cited by 622
New insights on the role of microglia in synaptic pruning in health and disease
Hong, S., Dissing-Olesen, L., & Stevens, B. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2015.12.004 · Cited by 557
Oxidative stress in the progression of Alzheimer disease in the frontal cortex
Ansari, M. A., & Scheff, S. W. (2010) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181cb5af4 · Cited by 605
Slow wave sleep disruption increases cerebrospinal fluid amyloid-β levels
Ju, Y.-E. S., Ooms, S. J., Sutphen, C., Macauley, S. L., Zangrilli, M. A., Jerome, G., Fagan, A. M., Mignot, E., Zempel, J. M., Claassen, J. A. H. R., et al. (2017) · Brain · doi:10.1093/brain/awx148 · Cited by 604
Self-citationSuppression of glymphatic fluid transport in a mouse model of Alzheimer's disease
Peng, W., Achariyar, T. M., Li, B., Liao, Y., Mestre, H., Hitomi, E., Regan, S., Kasper, T., Peng, S., Ding, F., et al. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.05.015 · Cited by 580
The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia
Iadecola, C. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0718-6 · Cited by 557
The road to restoring neural circuits for the treatment of Alzheimer's disease
Canter, R. G., Penney, J., & Tsai, L.-H. (2016) · Nature · doi:10.1038/nature20412 · Cited by 565
Roh, 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
Self-citationReiman, 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
The Alzheimer's disease Beta-secretase enzyme, BACE1
Cole, S. L., & Vassar, R. (2007) · Molecular Neurodegeneration · doi:10.1186/1750-1326-2-22 · Cited by 550
Sleep, circadian rhythms, and the pathogenesis of Alzheimer disease
Musiek, E. S., Xiong, D. D., & Holtzman, D. M. (2015) · Experimental & Molecular Medicine · doi:10.1038/emm.2014.121 · Cited by 529
Self-citationBiomarkers 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
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Liu, J., Chang, L., Song, Y., Li, H., & Wu, Y. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00043 · Cited by 535
Danysz, W., & Parsons, C. G. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.02057.x · Cited by 500
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Abramov, E., Dolev, I., Fogel, H., Ciccotosto, G. D., Ruff, E., & Slutsky, I. (2009) · Nature Neuroscience · doi:10.1038/nn.2433 · Cited by 499
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Janelidze, S., Zetterberg, H., Mattsson, N., Palmqvist, S., Vanderstichele, H., Lindberg, O., van Westen, D., Stomrud, E., Minthon, L., Blennow, K., et al. (2016) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.274 · Cited by 456
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Karch, C. M., Cruchaga, C., & Goate, A. M. (2014) · Neuron · doi:10.1016/j.neuron.2014.05.041 · Cited by 473
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Sheng, M., Sabatini, B. L., & Sudhof, T. C. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005777 · Cited by 436
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Ferreira, S. T., & Klein, W. L. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.08.003 · Cited by 442
Ooms, S., Overeem, S., Besse, K., Rikkert, M. O., Verbeek, M., & Claassen, J. A. H. R. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2014.1173 · Cited by 438
Wang, C., Najm, R., Xu, Q., Jeong, D.-E., Walker, D., Balestra, M. E., Yoon, S. Y., Yuan, H., Li, G., Miller, Z. A., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0004-z · Cited by 428
Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide
Hu, X., Crick, S. L., Bu, G., Frieden, C., Pappu, R. V., & Lee, J.-M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911281106 · Cited by 426
Alzheimer's disease: connecting findings from graph theoretical studies of brain networks
Tijms, B. M., Wink, A. M., de Haan, W., van der Flier, W. M., Stam, C. J., Scheltens, P., & Barkhof, F. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.02.020 · Cited by 416
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Lanctôt, K. L., Amatniek, J., Ancoli‐Israel, S., Arnold, S. E., Ballard, C., Cohen‐Mansfield, J., Ismail, Z., Lyketsos, C., Miller, D. S., Musiek, E., et al. (2017) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2017.07.001 · Cited by 395
Spatial correlation between brain aerobic glycolysis and amyloid-β (Aβ) deposition
Vlassenko, A. G., Vaishnavi, S. N., Couture, L., Sacco, D., Shannon, B. J., Mach, R. H., Morris, J. C., Raichle, M. E., & Mintun, M. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010461107 · Cited by 404
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Benzinger, T. L. S., Blazey, T., Jack, C. R., Koeppe, R. A., Su, Y., Xiong, C., Raichle, M. E., Snyder, A. Z., Ances, B. M., Bateman, R. J., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1317918110 · Cited by 391
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
Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease
Gouras, G. K., Tampellini, D., Takahashi, R. H., & Capetillo-Zarate, E. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0679-9 · Cited by 372
Cirrito, J. R., Disabato, B. M., Restivo, J. L., Verges, D. K., Goebel, W. D., Sathyan, A., Hayreh, D., D'Angelo, G., Benzinger, T., Yoon, H., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1107411108 · Cited by 377
Self-citationAmyloid beta from axons and dendrites reduces local spine number and plasticity
Wei, W., Nguyen, L. N., Kessels, H. W., Hagiwara, H., Sisodia, S., & Malinow, R. (2010) · Nature Neuroscience · doi:10.1038/nn.2476 · Cited by 357
Lehmann, M., Ghosh, P. M., Madison, C., Laforce, R., Corbetta-Rastelli, C., Weiner, M. W., Greicius, M. D., Seeley, W. W., Gorno-Tempini, M. L., Rosen, H. J., et al. (2013) · Brain · doi:10.1093/brain/aws327 · Cited by 325
Harris, J. A., Devidze, N., Verret, L., Ho, K., Halabisky, B., Thwin, M. T., Kim, D., Hamto, P., Lo, I., Yu, G.-Q., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.10.020 · Cited by 319
The Physiological Roles of Amyloid-β Peptide Hint at New Ways to Treat Alzheimer's Disease
Brothers, H. M., Gosztyla, M. L., & Robinson, S. R. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00118 · Cited by 314
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Gulisano, W., Maugeri, D., Baltrons, M. A., Fà, M., Amato, A., Palmeri, A., D’Adamio, L., Grassi, C., Devanand, D. P., Honig, L. S., et al. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179935 · Cited by 313
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Chen, X., & Holtzman, D. M. (2022) · Immunity · doi:10.1016/j.immuni.2022.10.016 · Cited by 297
Self-citationβ-Amyloid, Blood Vessels, and Brain Function
Smith, E. E., & Greenberg, S. M. (2009) · Stroke · doi:10.1161/strokeaha.108.536839 · Cited by 293
Amyloid-β Dynamics Correlate with Neurological Status in the Injured Human Brain
Brody, D. L., Magnoni, S., Schwetye, K. E., Spinner, M. L., Esparza, T. J., Stocchetti, N., Zipfel, G. J., & Holtzman, D. M. (2008) · Science · doi:10.1126/science.1161591 · Cited by 295
Self-citationGlial activation and inflammation along the Alzheimer’s disease continuum
Nordengen, K., Kirsebom, B.-E., Henjum, K., Selnes, P., Gísladóttir, B., Wettergreen, M., Torsetnes, S. B., Grøntvedt, G. R., Waterloo, K. K., Aarsland, D., et al. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1399-2 · Cited by 274
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Kanekiyo, T., Cirrito, J. R., Liu, C.-C., Shinohara, M., Li, J., Schuler, D. R., Shinohara, M., Holtzman, D. M., & Bu, G. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3487-13.2013 · Cited by 280
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Chandra, S., Sisodia, S. S., & Vassar, R. J. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00595-7 · Cited by 278
Xiang, X., Wind, K., Wiedemann, T., Blume, T., Shi, Y., Briel, N., Beyer, L., Biechele, G., Eckenweber, F., Zatcepin, A., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abe5640 · Cited by 268
Molecular mechanisms of cognitive dysfunction following traumatic brain injury
Walker, K. R., & Tesco, G. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00029 · Cited by 265
Fluctuations of CSF amyloid-β levels: Implications for a diagnostic and therapeutic biomarker
Bateman, R. J., Wen, G., Morris, J. C., & Holtzman, D. M. (2007) · Neurology · doi:10.1212/01.wnl.0000256043.50901.e3 · Cited by 260
Self-citationThe olfactory bulb as the entry site for prion-like propagation in neurodegenerative diseases
Rey, N. L., Wesson, D. W., & Brundin, P. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.12.013 · Cited by 257
Brain Perivascular Macrophages Initiate the Neurovascular Dysfunction of Alzheimer Aβ Peptides
Park, L., Uekawa, K., Garcia-Bonilla, L., Koizumi, K., Murphy, M., Pistik, R., Younkin, L., Younkin, S., Zhou, P., Carlson, G., et al. (2017) · Circulation Research · doi:10.1161/circresaha.117.311054 · Cited by 259
APOE mediated neuroinflammation and neurodegeneration in Alzheimer’s disease
Parhizkar, S., & Holtzman, D. M. (2022) · Seminars in Immunology · doi:10.1016/j.smim.2022.101594 · Cited by 255
Self-citationBi, D., Wen, L., Wu, Z., & Shen, Y. (2020) · Alzheimer's & Dementia · doi:10.1002/alz.12088 · Cited by 232
Kemppainen, N. M., Aalto, S., Karrasch, M., Någren, K., Savisto, N., Oikonen, V., Viitanen, M., Parkkola, R., & Rinne, J. O. (2008) · Annals of Neurology · doi:10.1002/ana.21212 · Cited by 239
Cerebrospinal Fluid Clearance in Alzheimer Disease Measured with Dynamic PET
de Leon, M. J., Li, Y., Okamura, N., Tsui, W. H., Saint-Louis, L. A., Glodzik, L., Osorio, R. S., Fortea, J., Butler, T., Pirraglia, E., et al. (2017) · Journal of Nuclear Medicine · doi:10.2967/jnumed.116.187211 · Cited by 246
Kandalepas, P. C., Sadleir, K. R., Eimer, W. A., Zhao, J., Nicholson, D. A., & Vassar, R. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1152-3 · Cited by 240
Bossers, K., Wirz, K. T. S., Meerhoff, G. F., Essing, A. H. W., van Dongen, J. W., Houba, P., Kruse, C. G., Verhaagen, J., & Swaab, D. F. (2010) · Brain · doi:10.1093/brain/awq258 · Cited by 230
Analyzing dendritic spine pathology in Alzheimer’s disease: Problems and opportunities
Dorostkar, M. M., Zou, C., Blazquez-Llorca, L., & Herms, J. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1449-5 · Cited by 235
Deshpande, A., Kawai, H., Metherate, R., Glabe, C. G., & Busciglio, J. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5980-08.2009 · Cited by 232
Human secreted tau increases amyloid-beta production
Bright, J., Hussain, S., Dang, V., Wright, S., Cooper, B., Byun, T., Ramos, C., Singh, A., Parry, G., Stagliano, N., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.09.007 · Cited by 230
Sanchez-Varo, R., Trujillo-Estrada, L., Sanchez-Mejias, E., Torres, M., Baglietto-Vargas, D., Moreno-Gonzalez, I., De Castro, V., Jimenez, S., Ruano, D., Vizuete, M., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0896-x · Cited by 222
Lifespan brain activity, β-amyloid, and Alzheimer's disease
Jagust, W. J., & Mormino, E. C. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.09.004 · Cited by 221
“Initial research found that neural activity modulates the release of cleavage products of the amyloid precursor protein [1], and that Aβ secretion could be affected by manipulation of neural activity [2] through a process that involves synaptic exocytosis (the process whereby cells release substances through the cell…”
Kang, J.-E., Cirrito, J. R., Dong, H., Csernansky, J. G., & Holtzman, D. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700148104 · Cited by 219
Dendritic Spine Pathology in Neurodegenerative Diseases
Herms, J., & Dorostkar, M. M. (2016) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044216 · Cited by 201
The Relationship between Obstructive Sleep Apnea and Alzheimer’s Disease
Andrade, A. G., Bubu, O. M., Varga, A. W., & Osorio, R. S. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179936 · Cited by 216
Early Alzheimer’s disease pathology in human cortex involves transient cell states
Gazestani, V., Kamath, T., Nadaf, N. M., Dougalis, A., Burris, S. J., Rooney, B., Junkkari, A., Vanderburg, C., Pelkonen, A., Gomez-Budia, M., et al. (2023) · Cell · doi:10.1016/j.cell.2023.08.005 · Cited by 209
Common dysregulation network in the human prefrontal cortex underlies two neurodegenerative diseases
Narayanan, M., Huynh, J. L., Wang, K., Yang, X., Yoo, S., McElwee, J., Zhang, B., Zhang, C., Lamb, J. R., Xie, T., et al. (2014) · Molecular Systems Biology · doi:10.15252/msb.20145304 · Cited by 208
APOE2 enhances neuroprotection against Alzheimer’s disease through multiple molecular mechanisms
Conejero-Goldberg, C., Gomar, J. J., Bobes-Bascaran, T., Hyde, T. M., Kleinman, J. E., Herman, M. M., Chen, S., Davies, P., & Goldberg, T. E. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.194 · Cited by 199
Zhao, W.-Q., Santini, F., Breese, R., Ross, D., Zhang, X. D., Stone, D. J., Ferrer, M., Townsend, M., Wolfe, A. L., Seager, M. A., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.057182 · Cited by 188
Nuriel, T., Angulo, S. L., Khan, U., Ashok, A., Chen, Q., Figueroa, H. Y., Emrani, S., Liu, L., Herman, M., Barrett, G., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01444-0 · Cited by 181
Beagle, A. J., Darwish, S. M., Ranasinghe, K. G., La, A. L., Karageorgiou, E., & Vossel, K. A. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-170031 · Cited by 173
The sleep–wake Cycle and Alzheimer’s Disease: What do We know?
Lim, M. M., Gerstner, J. R., & Holtzman, D. M. (2014) · Neurodegenerative Disease Management · doi:10.2217/nmt.14.33 · Cited by 168
Self-citationSleep Interacts with Aβ to Modulate Intrinsic Neuronal Excitability
Tabuchi, M., Lone, S. R., Liu, S., Liu, Q., Zhang, J., Spira, A. P., & Wu, M. N. (2015) · Current Biology · doi:10.1016/j.cub.2015.01.016 · Cited by 165
Harris, S. S., Wolf, F., De Strooper, B., & Busche, M. A. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.005 · Cited by 161
More than cholesterol transporters: lipoprotein receptors in CNS function and neurodegeneration
Lane-Donovan, C., Philips, G. T., & Herz, J. (2014) · Neuron · doi:10.1016/j.neuron.2014.08.005 · Cited by 158
Metadata
- Authors
- Cirrito, J. R., Yamada, K. A., Finn, M. B., Sloviter, R. S., Bales, K. R., May, P. C., Schoepp, D. D., Paul, S. M., Mennerick, S., & Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- University of Arizona (US)
- Eli Lilly (United States) (US)
- Corresponding author
- Holtzman, David M.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 48
- Issue
- 6
- Pages
- 913-922
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2046952010
- Cited by
- 1,265
- References
- 38
- Citations by year
- 2026: 34 · 2025: 62 · 2024: 76 · 2023: 69 · 2022: 62 · 2021: 83 · 2020: 93 · 2019: 76 · 2018: 58 · 2017: 85 · 2016: 52 · 2015: 62 · 2014: 81 · 2013: 70 · 2012: 69
- FWCI
- 15.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG11355, AG13956, P01AG011355)
- National Institute on Drug Abuse (DA70261)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta, synaptic activity, interstitial fluid, Alzheimer's disease, synaptic vesicle exocytosis, amyloid-beta metabolism, microdialysis, field potential recording
- MeSH terms
- Action Potentials, Alzheimer Disease, Animals, Brain, Exocytosis, Female, Hippocampus, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Degeneration, Synaptic Transmission, Organ Culture Techniques, Synaptic Vesicles, Amyloid beta-Peptides, Microdialysis, Presynaptic Terminals, Mice, Knockout, Patch-Clamp Techniques, Perforant Pathway, Extracellular Fluid, Mice, Plaque, Amyloid
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