Synaptic Activity Regulates Interstitial Fluid Amyloid-β Levels In Vivo

Cirrito, John R.; Yamada, Kelvin A.; Finn, Mary Beth; Sloviter, Robert S.; Bales, Kelly R.; May, Patrick C.; Schoepp, Darryle D.; Paul, Steven M.; Mennerick, Steven; Holtzman, David M.

doi:10.1016/j.neuron.2005.10.028

Cited by 1,265Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration Mechanisms

Synaptic Activity Regulates Interstitial Fluid Amyloid-β Levels In Vivo

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Cirrito, John R., Yamada, Kelvin A., Finn, Mary Beth, Sloviter, Robert S., Bales, Kelly R., May, Patrick C., Schoepp, Darryle D., Paul, Steven M. +2 more·2005·Neuron

DOI 10.1016/j.neuron.2005.10.028

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Abstract

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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Most neuronal amyloid beta is secreted at presynaptic terminals, thus favouring plaque deposition in the grey matter.
“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]
Depolarization and subsequent synaptic transmission causes Aβ to be produced presynaptically and then secreted into the brain extracellular fluid or interstitial fluid (ISF).
“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]
Tetrodotoxin (TTX) dramatically reduces neuronal activity and ISF Aβ levels in vivo.
“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]
Synaptic activity is one key regulator of brain Aβ production.
“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]
Synaptic activity regulates Aβ levels through a presynaptic mechanism that is dependent on APP endocytosis and cleavage.
“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]

APP and Aβ homeostasis are exquisitely regulated processes, and bioenergetic metabolism regulates these processes.
“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]
Although aggregates have been considered toxic, soluble Aβ at physiological levels has biological functions, including enhancement of long-term potentiation, stimulation of neuronal differentiation, improvement of brain recovery from injuries, inhibition of oxidative stress, antimicrobial activity, and tumor suppression.
“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]
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.
“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
Synaptic activity increases secretion of Aβ in hippocampal slices and living rodent brain.
“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]

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 · see citing works
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 · see citing works
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 · see citing works
Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory
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 · see citing works
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 · see citing works
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 1,200 · see citing works
Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease
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× · see citing works
“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).”
Background
Evidence 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 989 · see citing works
Environmental 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 · see citing works
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 · see citing works
Self-citation
Environmental Enrichment Mitigates Cognitive Deficits in a Mouse Model of Alzheimer's Disease
Jankowsky, J. L., Melnikova, T., Fadale, D. J., Xu, G. M., Slunt, H. H., Gonzales, V., Younkin, L. H., Younkin, S. G., Borchelt, D. R., & Savonenko, A. V. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.5080-04.2005 · Cited by 517 · see citing works
ApoE and Clusterin Cooperatively Suppress Aβ Levels and Deposition
DeMattos, R. B., Cirrito, J. R., Parsadanian, M., May, P. C., O'Dell, M. A., Taylor, J. W., Harmony, J. A. K., Aronow, B. J., Bales, K. R., Paul, S. M., et al. (2004) · Neuron · doi:10.1016/s0896-6273(03)00850-x · Cited by 459 · see citing works
Self-citation
In Vivo Assessment of Brain Interstitial Fluid with Microdialysis Reveals Plaque-Associated Changes in Amyloid-β Metabolism and Half-Life
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-citation
Evidence for Seeding of β-Amyloid by Intracerebral Infusion of Alzheimer Brain Extracts in β-Amyloid Precursor Protein-Transgenic Mice
Kane, M. D., Lipinski, W. J., Callahan, M. J., Bian, F., Durham, R. A., Schwarz, R. D., Roher, A. E., & Walker, L. C. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-10-03606.2000 · Cited by 394 · see citing works
Evidence That Synaptically Released β-Amyloid Accumulates as Extracellular Deposits in the Hippocampus of Transgenic Mice
Lazarov, O., Lee, M., Peterson, D. A., & Sisodia, S. S. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-22-09785.2002 · Cited by 302 · see citing works
Functional neuroimaging studies of encoding, priming, and explicit memory retrieval
Buckner, R. L., & Koutstaal, W. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.3.891 · Cited by 287 · see citing works
Alzheimer Amyloid Protein Precursor in the Rat Hippocampus: Transport and Processing through the Perforant Path
Buxbaum, J. D., Thinakaran, G., Koliatsos, V. E., O’Callahan, J., Slunt, H. H., Price, D. L., & Sisodia, S. S. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-23-09629.1998 · Cited by 266 · see citing works
Voluntary exercise protects against stress-induced decreases in brain-derived neurotrophic factor protein expression
Adlard, P. A., & Cotman, C. W. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2003.12.039 · Cited by 265 · see citing works
Release of amyloid beta-protein precursor derivatives by electrical depolarization of rat hippocampal slices
Nitsch, R. M., Farber, S. A., Growdon, J. H., & Wurtman, R. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.11.5191 · Cited by 244 · see citing works
Environmental Enrichment Exacerbates Amyloid Plaque Formation in a Transgenic Mouse Model of Alzheimer Disease
Jankowsky, J. L., Xu, G. M., Fromholt, D., Gonzales, V., & Borchelt, D. (2003) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/62.12.1220 · Cited by 240 · see citing works
alpha-Latrotoxin and its receptors: neurexins and CIRL/latrophilins.
Südhof, T. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.933 · Cited by 215 · see citing works
Senile plaques in temporal lobe epilepsy
Mackenzie, I. R. A., & Miller, L. A. (1994) · Acta Neuropathologica · doi:10.1007/bf00294177 · Cited by 168 · see citing works
Apolipoprotein E Markedly Facilitates Age-Dependent Cerebral Amyloid Angiopathy and Spontaneous Hemorrhage in Amyloid Precursor Protein Transgenic Mice
Fryer, J. D., Taylor, J. W., DeMattos, R. B., Bales, K. R., Paul, S. M., Parsadanian, M., & Holtzman, D. M. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-21-07889.2003 · Cited by 160 · see citing works
Self-citation
Extracellular amyloid formation and associated pathology in neural grafts
Meyer‐Luehmann, M., Stalder, M., Herzig, M. C., Kaeser, S. A., Kohler, E., Pfeifer, M., Boncristiano, S., Mathews, P. M., Mercken, M. H., Abramowski, D., et al. (2003) · Nature Neuroscience · doi:10.1038/nn1022 · Cited by 133 · see citing works
Studies of Aβ Pharmacodynamics in the Brain, Cerebrospinal Fluid, and Plasma in Young (Plaque-Free) Tg2576 Mice Using the γ-Secretase Inhibitor N2-[(2 S)-2-(3,5-Difluorophenyl)-2-hydroxyethanoyl]-N1-[(7 S)-5-methyl-6-oxo-6,7-dihydro-5 H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY-411575)
Lanz, T. A., Hosley, J. D., Adams, W. J., & Merchant, K. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.060715 · Cited by 130 · see citing works
Trafficking of Cell-Surface β-Amyloid Precursor Protein: Evidence that a Sorting Intermediate Participates in Synaptic Vesicle Recycling
Marquez-Sterling, N. R., Lo, A., Sisodia, S. S., & Koo, E. H. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-01-00140.1997 · Cited by 124 · see citing works
Disruption of Corticocortical Connections Ameliorates Amyloid Burden in Terminal Fields in a Transgenic Model of Aβ Amyloidosis
Sheng, J. G., Price, D. L., & Koliatsos, V. E. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-22-09794.2002 · Cited by 124 · see citing works
GABAergic and glycinergic neurons projecting to the trigeminal motor nucleus: A double labeling study in the rat
Li, Y., Takada, M., Kaneko, T., & Mizuno, N. (1996) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19960930)373:4 · Cited by 112 · see citing works
β-Amyloid Directly Inhibits Human α4β2-Nicotinic Acetylcholine Receptors Heterologously Expressed in Human SH-EP1 Cells
Wu, J., Kuo, Y., George, A. A., Xu, L., Hu, J., & Lukas, R. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400335200 · Cited by 111 · see citing works
Treatment with the selective muscarinic ml agonist talsaclidine decreases cerebrospinal fluid levels of Aβ42in patients with Alzheimer's disease
Höck, C., Maddalena, A. S., Raschig, A., Müller-Spahn, F., Eschweiler, G. W., Huger, K., Hewer, I., Hampel, H. J., Müller-Thornsen, T., Oertel, W. H., et al. (2003) · Amyloid · doi:10.3109/13506120308995249 · Cited by 110 · see citing works
Tetanus Toxin Blocks the Exocytosis of Synaptic Vesicles Clustered at Synapses But Not of Synaptic Vesicles in Isolated Axons
Verderio, C., Coco, S., Bacci, A., Rossetto, O., Camilli, P. V. D., Montecucco, C., & Matteoli, M. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-16-06723.1999 · Cited by 96 · see citing works
Increased apolipoprotein E ϵ4 in epilepsy with senile plaques
Gouras, G. K., Relkin, N. R., Sweeney, D. A., Muñoz, D. G., Mackenzie, I. R., & Gandy, S. (1997) · Annals of Neurology · doi:10.1002/ana.410410317 · Cited by 85 · see citing works
Alzheimer Amyloid Protein Precursor Is Localized in Nerve Terminal Preparations to Rab5-containing Vesicular Organelles Distinct from Those Implicated in the Synaptic Vesicle Pathway
Ikin, A. F., Annaert, W. G., Takei, K., Camilli, P. V. D., Jahn, R., Greengard, P., & Buxbaum, J. D. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.50.31783 · Cited by 83 · see citing works
Post-translational Processing and Turnover Kinetics of Presynaptically Targeted Amyloid Precursor Superfamily Proteins in the Central Nervous System
Lyckman, A. W., Confaloni, A., Thinakaran, G., et al. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.18.11100 · Cited by 78 · see citing works
Characterization of the Tetanus Toxin Model of Refractory Focal Neocortical Epilepsy in the Rat
Nilsen, K. E., Walker, M. C., & Cock, H. R. (2005) · Epilepsia · doi:10.1111/j.0013-9580.2005.26004.x · Cited by 60 · see citing works
Muscarine enhances soluble amyloid precursor protein secretion in human neuroblastoma SH-SY5Y by a pathway dependent on protein kinase Cα, src-tyrosine kinase and extracellular signal-regulated kinase but not phospholipase C
Canet-Aviles, R., Anderton, M. J., Hooper, N. M., Turner, A. J., & Vaughan, P. F. T. (2002) · Molecular Brain Research · doi:10.1016/s0169-328x(02)00184-5 · Cited by 52 · see citing works
Reduction of cortical amyloid β levels in guinea pig brain after systemic administration of physostigmine
Beach, T. G., Kuo, Y., Schwab, C., Walker, D. G., & Roher, A. E. (2001) · Neuroscience Letters · doi:10.1016/s0304-3940(01)02076-6 · Cited by 40 · see citing works
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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
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Jagust, W. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0067-3 · Cited by 604 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Self-citation
Suppression 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 · see citing works
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 · see citing works
Disruption of the Sleep-Wake Cycle and Diurnal Fluctuation of β-Amyloid in Mice with Alzheimer’s Disease Pathology
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 · see citing works
Self-citation
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 · see citing works
Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer's disease in the presenilin 1 E280A kindred: a case-control study
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 · see citing works
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 · see citing works
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 · see citing works
Self-citation
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 · see citing works
The Role of NMDA Receptors in Alzheimer’s Disease
Liu, J., Chang, L., Song, Y., Li, H., & Wu, Y. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00043 · Cited by 535 · see citing works
Alzheimer's disease, β‐amyloid, glutamate, NMDA receptors and memantine – searching for the connections
Danysz, W., & Parsons, C. G. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.02057.x · Cited by 500 · see citing works
Amyloid-β as a positive endogenous regulator of release probability at hippocampal synapses
Abramov, E., Dolev, I., Fogel, H., Ciccotosto, G. D., Ruff, E., & Slutsky, I. (2009) · Nature Neuroscience · doi:10.1038/nn.2433 · Cited by 499 · see citing works
<scp>CSF</scp> Aβ42/Aβ40 and Aβ42/Aβ38 ratios: better diagnostic markers of Alzheimer disease
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 · see citing works
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 · see citing works
Synapses and Alzheimer's Disease
Sheng, M., Sabatini, B. L., & Sudhof, T. C. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005777 · Cited by 436 · see citing works
Effect of 1 Night of Total Sleep Deprivation on Cerebrospinal Fluid β-Amyloid 42 in Healthy Middle-Aged Men: A Randomized Clinical Trial
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 · see citing works
The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease
Ferreira, S. T., & Klein, W. L. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.08.003 · Cited by 442 · see citing works
Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector
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 · see citing works
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 · see citing works
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 · see citing works
Neuropsychiatric signs and symptoms of Alzheimer's disease: New treatment paradigms
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 · see citing works
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 · see citing works
Regional variability of imaging biomarkers in autosomal dominant Alzheimer's disease
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 · see citing works
Self-citation
Effect 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
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 · see citing works
Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans
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 370 · see citing works
Self-citation
Amyloid 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 · see citing works
Diverging patterns of amyloid deposition and hypometabolism in clinical variants of probable Alzheimer's disease
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 · see citing works
Transsynaptic progression of amyloid-β-induced neuronal dysfunction within the entorhinal-hippocampal network
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 · see citing works
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 · see citing works
Role of Amyloid-β and Tau Proteins in Alzheimer’s Disease: Confuting the Amyloid Cascade
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 · see citing works
Emerging roles of innate and adaptive immunity in Alzheimer’s disease
Chen, X., & Holtzman, D. M. (2022) · Immunity · doi:10.1016/j.immuni.2022.10.016 · Cited by 297 · see citing works
Self-citation
β-Amyloid, Blood Vessels, and Brain Function
Smith, E. E., & Greenberg, S. M. (2009) · Stroke · doi:10.1161/strokeaha.108.536839 · Cited by 293 · see citing works
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 · see citing works
Self-citation
Glial 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 · see citing works
Neuronal Clearance of Amyloid-β by Endocytic Receptor LRP1
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 · see citing works
Self-citation
The gut microbiome in Alzheimer’s disease: what we know and what remains to be explored
Chandra, S., Sisodia, S. S., & Vassar, R. J. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00595-7 · Cited by 278 · see citing works
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 · see citing works
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 · see citing works
Self-citation
The 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 · see citing works
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 · see citing works
GABAergic dysfunction in excitatory and inhibitory (E/I) imbalance drives the pathogenesis of Alzheimer's disease
Bi, D., Wen, L., Wu, Z., & Shen, Y. (2020) · Alzheimer's & Dementia · doi:10.1002/alz.12088 · Cited by 232 · see citing works
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 · see citing works
Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer's disease
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 · see citing works
The Alzheimer’s β-secretase BACE1 localizes to normal presynaptic terminals and to dystrophic presynaptic terminals surrounding amyloid plaques
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 · see citing works
Concerted changes in transcripts in the prefrontal cortex precede neuropathology in Alzheimer's disease
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 · see citing works
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 · see citing works
A Role for Synaptic Zinc in Activity-Dependent Aβ Oligomer Formation and Accumulation at Excitatory Synapses
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 · see citing works
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 · see citing works
Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer’s mice hippocampus
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 · see citing works
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 · see citing works
Acute stress increases interstitial fluid amyloid-β via corticotropin-releasing factor and neuronal activity
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Inhibition of Calcineurin-mediated Endocytosis and α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors Prevents Amyloid β Oligomer-induced Synaptic Disruption
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 · see citing works
Neuronal hyperactivity due to loss of inhibitory tone in APOE4 mice lacking Alzheimer’s disease-like pathology
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 · see citing works
Relative incidence of seizures and myoclonus in Alzheimer’s disease, dementia with lewy bodies, and frontotemporal dementia.
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 · see citing works
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 · see citing works
Self-citation
Sleep 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 · see citing works
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 · see citing works
Tipping the Scales: Peptide-Dependent Dysregulation of Neural Circuit Dynamics in Alzheimer’s Disease
Harris, S. S., Wolf, F., De Strooper, B., & Busche, M. A. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.005 · Cited by 161 · see citing works
Reduced Posterior Cingulate Mitochondrial Activity in Expired Young Adult Carriers of the APOE ε4 Allele, the Major Late-Onset Alzheimer's Susceptibility Gene
Valla, J., Yaari, R., Wolf, A. B., Kusne, Y., Beach, T. G., Roher, A. E., Corneveaux, J. J., Huentelman, M. J., Caselli, R. J., & Reiman, E. M. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100129 · Cited by 150 · see citing works
APP Homodimers Transduce an Amyloid-β-Mediated Increase in Release Probability at Excitatory Synapses
Fogel, H., Frere, S., Segev, O., Bharill, S., Shapira, I., Gazit, N., O’Malley, T., Slomowitz, E., Berdichevsky, Y., Walsh, D. M., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.04.024 · Cited by 138 · 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
Self-citation
Cerebrovascular Dysfunction in Amyloid Precursor Protein Transgenic Mice: Contribution of Soluble and Insoluble Amyloid-β Peptide, Partial Restoration via γ-Secretase Inhibition
Han, B. H., Zhou, M.-L., Abousaleh, F., Brendza, R. P., Dietrich, H. H., Koenigsknecht-Talboo, J., Cirrito, J. R., Milner, E., Holtzman, D. M., & Zipfel, G. J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4686-08.2008 · Cited by 138 · see citing works
Self-citation

Microdialysis methodology for the measurement of dermal interstitial fluid in humans
Krogstad, A., Jansson, P., GISSLÉN, P., & Lönnroth, P. (1996) · British Journal of Dermatology · doi:10.1046/j.1365-2133.1996.d01-893.x · Cited by 98 · see citing works
In Vivo Assessment of Brain Interstitial Fluid with Microdialysis Reveals Plaque-Associated Changes in Amyloid-β Metabolism and Half-Life
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-citation
A Modified in vivo Flow Variation Technique of Microdialysis for Sampling Uremic Toxins in the Subcutaneous Interstitial Compartment
Ebah, L. M., Brenchley, P. E., Coupes, B. M., et al. (2011) · Blood Purification · doi:10.1159/000324207 · Cited by 11 · see citing works
P2‐458: NPT001 reduces Aβ plaque without altering brain interstitial fluid Aβ levels in aged Tg2576 mice
Gannon, K. S., Restivo, J. L., Fisher, R. A., et al. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2011.05.1330
Validation of the ‘internal reference technique’ for calibrating microdialysis catheters in situ
Lönnroth, P., & Strindberg, L. (1995) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1995.tb09875.x · Cited by 87 · see citing works

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: Cirrito, John R.
Finn, Mary Beth
Sloviter, Robert S.
May, Patrick C.
Paul, Steven M.
Mennerick, Steven
Holtzman, David M.
Venue: Neuron
Publisher: Elsevier BV
Published: 2005-12
Volume: 48
Issue: 6
Pages: 913-922
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/j.neuron.2005.10.028
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2785 d)
Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (AG11355, AG13956, P01AG011355)
National Institute on Drug Abuse (DA70261)
Topics: Health Sciences › Medicine › Physiology › 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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Synaptic Activity Regulates Interstitial Fluid Amyloid-β Levels In Vivo

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