Amyloid-β 1–42 Slows Clearance of Synaptically Released Glutamate by Mislocalizing Astrocytic GLT-1
Open accessAbstract
GLT-1, the major glutamate transporter in the adult brain, is abundantly expressed in astrocytic processes enveloping synapses. By limiting glutamate escape into the surrounding neuropil, GLT-1 preserves the spatial specificity of synaptic signaling. Here we show that the amyloid-β peptide Aβ 1–42 markedly prolongs the extracellular lifetime of synaptically released glutamate by reducing GLT-1 surface expression in mouse astrocytes and that this effect is prevented by the vitamin E derivative Trolox. These findings indicate that astrocytic glutamate transporter dysfunction may play an important role in the pathogenesis of Alzheimer's disease and suggest possible mechanisms by which several current treatment strategies could protect against the disease.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Aβ42 impairs the function of GLT-1 and GLAST in hippocampal astrocytes.
“while Aβ42 was shown to impair the function of the excitatory amino acid transporter (GLT-1) and the glutamate/aspartate transporter (GLAST) in hippocampal astrocytes [12].”
From Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease (2022) · cites this paper as [12]
The Results (page not provided) show that Aβ1–42 reduced GLT-1 surface expression and slowed clearance of synaptically released glutamate. They do not show impaired GLAST function: GLAST surface expression was unchanged after treatment. The claim is supported for GLT-1, but not for GLAST. (LLM, conf=0.91)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Statistical Principles in Experimental Design
Green, P. E., Winer, B. J., Brown, D. R., & Michels, K. M. (1992) · Journal of Marketing Research · doi:10.2307/3172747 · Cited by 4,333 · see citing works
Epilepsy and Exacerbation of Brain Injury in Mice Lacking the Glutamate Transporter GLT-1
Tanaka, K., Watase, K., Manabe, T., Yamada, K., Watanabe, M., Takahashi, K., Iwama, H., Nishikawa, T., Ichihara, N., Kikuchi, T., et al. (1997) · Science · doi:10.1126/science.276.5319.1699 · Cited by 1,755 · see citing works
Primary structure and functional characterization of a high-affinity glutamate transporter
Kanai, Y., & Hediger, M. A. (1992) · Nature · doi:10.1038/360467a0 · Cited by 1,339 · see citing works
In vitro characterization of conditions for amyloid-β peptide oligomerization and fibrillogenesis
Stine, W. B., Dahlgren, K. N., Krafft, G. A., & LaDu, M. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210207200 · Cited by 1,015 · see citing works
Chaudhry, F. A., Lehre, K. P., Campagne, M. V. L., Ottersen, O. P., Danbolt, N. C., & Storm‐Mathisen, J. (1995) · Neuron · doi:10.1016/0896-6273(95)90158-2 · Cited by 827 · see citing works
Felipo, V., & Butterworth, R. F. (2002) · Progress in Neurobiology · doi:10.1016/s0301-0082(02)00019-9 · Cited by 626 · see citing works
Neuronal Regulation of Glutamate Transporter Subtype Expression in Astrocytes
Swanson, R. A., Liu, J., Miller, J. W., Rothstein, J. D., Farrell, K., Stein-Behrens, B., & Longuemare, M. C. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-03-00932.1997 · Cited by 500 · see citing works
Brain Glutamate Transporter Proteins Form Homomultimers
Haugeto, Ø., Ullensvang, K., Levy, L. M., Chaudhry, F. A., Honoré, T., Nielsen, M., Lehre, K. P., & Danbolt, N. C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.44.27715 · Cited by 489 · see citing works
Transporters Buffer Synaptically Released Glutamate on a Submillisecond Time Scale
Diamond, J. S., & Jahr, C. E. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-12-04672.1997 · Cited by 486 · see citing works
Self-citationDeficient glutamate tranport is associated with neurodegeneration in Alzheimer's disease
Masliah, E., Hansen, L., Alford, M., Deteresa, R., & Mallory, M. (1996) · Annals of Neurology · doi:10.1002/ana.410400512 · Cited by 476 · see citing works
Trotti, D., Danbolt, N. C., & Volterra, A. (1998) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(98)01230-9 · Cited by 469 · see citing works
Lauderback, C. M., Hackett, J. M., Huang, F. F., Keller, J. N., Szweda, L. I., Markesbery, W. R., & Butterfield, D. A. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00451.x · Cited by 464 · see citing works
Rukhsana Sultana, A., Debra Boyd-kimball, A., Poon, H. F., Cai, J., Pierce, W. M. J., Klein, J. B., Merchant, M. L., Markesbery, W. R., & Butterfield, D. A. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.09.021 · Cited by 334 · see citing works
Abdul, H. M., Sama, M. A., Furman, J. L., Mathis, D. M., Beckett, T. L., Weidner, A. M., Patel, E., Baig, I., Murphy, M. P., LeVine, H., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1064-09.2009 · Cited by 319 · see citing works
Jacob, C. P., Koutsilieri, E., Bartl, J., Neuen-Jacob, E., Arzberger, T., Zander, N., Ravid, R., Roggendorf, W., Riederer, P., & Grünblatt, E. (2007) · Journal of Alzheimer's Disease · doi:10.3233/jad-2007-11113 · Cited by 317 · see citing works
Voutsinos‐Porche, B., Bonvento, G., Tanaka, K., Steiner, P., Welker, E., Chatton, J., Magistretti, P. J., & Pellerin, L. (2003) · Neuron · doi:10.1016/s0896-6273(02)01170-4 · Cited by 293 · see citing works
Lipton, S. A. (2005) · Current Alzheimer Research · doi:10.2174/1567205053585846 · Cited by 256 · see citing works
Neuronal and Glial Glutamate Transporters Possess an SH‐based Redox Regulatory Mechanism
Trotti, D., Rizzini, B. L., Rossi, D., Haugeto, Ø., Racagni, G., Danbolt, N. C., & Volterra, A. (1997) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1997.tb01478.x · Cited by 178 · see citing works
Scimemi, A., Tian, H., & Diamond, J. S. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4845-09.2009 · Cited by 169 · see citing works
Self-citationGLT-1 Loss Accelerates Cognitive Deficit Onset in an Alzheimer's Disease Animal Model
Mookherjee, P., Green, P. S., Watson, G. S., Marques, M. A., Tanaka, K., Meeker, K. D., Meabon, J. S., Li, N., Zhu, P., Olson, V. G., et al. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110503 · Cited by 164 · see citing works
Self-citationDiamond, J. S. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.5125-04.2005 · Cited by 164 · see citing works
Self-citationSama, M. A., Mathis, D. M., Furman, J. L., Abdul, H. M., Artiushin, I. A., Kraner, S. D., & Norris, C. M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800148200 · Cited by 139 · see citing works
Quintanilla, R. A., Muñoz, F. J., Metcalfe, M., Hitschfeld, M., Olivares, G. H., Godoy, J. A., & Inestrosa, N. C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411936200 · Cited by 113 · see citing works
Tsvetkov, E., Shin, R.-M., & Bolshakov, V. Y. (2004) · Neuron · doi:10.1016/s0896-6273(03)00800-6 · Cited by 110 · see citing works
Aberrant Detergent-Insoluble Excitatory Amino Acid Transporter 2 Accumulates in Alzheimer Disease
Woltjer, R. L., Duerson, K. C., Fullmer, J. M., Mookherjee, P., Ryan, A. M., Montine, T. J., Kaye, J. A., Quinn, J. F., Silbert, L. C., Erten‐Lyons, D., et al. (2010) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181e24adb · Cited by 73 · see citing works
Self-citationde Villarreal, J. M., García‐Tardón, N., Ibáñez, I., Giménez, C., & Zafra, F. (2012) · Glia · doi:10.1002/glia.22354 · Cited by 53 · see citing works
Woltjer, R. L., Cimino, P. J., Boutté, A. M., Schantz, A. M., Montine, K. S., Larson, E. B., Bird, T. D., Quinn, J. F., Zhang, J., & Montine, T. J. (2005) · The FASEB Journal · doi:10.1096/fj.05-4263fje · Cited by 49 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994 · see citing works
Chronic Glutamate Toxicity in Neurodegenerative Diseases—What is the Evidence?
Lewerenz, J., & Maher, P. A. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00469 · Cited by 721 · see citing works
Banks, W. A., Gray, A. M., Erickson, M. A., Salameh, T. S., Damodarasamy, M., Sheibani, N., Meabon, J. S., Wing, E. E., Morofuji, Y., Cook, D. G., et al. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0434-1 · Cited by 636 · see citing works
Self-citationExtrasynaptic NMDA Receptor Involvement in Central Nervous System Disorders
Parsons, M. P., & Raymond, L. A. (2014) · Neuron · doi:10.1016/j.neuron.2014.03.030 · Cited by 555 · see citing works
Elusive roles for reactive astrocytes in neurodegenerative diseases
Ben Haim, L., Carrillo-de Sauvage, M.-A., Ceyzériat, K., & Escartin, C. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00278 · Cited by 453 · see citing works
Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration.
Andersen, J. V., Markussen, K., Jakobsen, E., Schousboe, A., Waagepetersen, H., Rosenberg, P., & Aldana, B. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108719 · Cited by 331 · see citing works
Beyond the neuron–cellular interactions early in Alzheimer disease pathogenesis
Henstridge, C. M., Hyman, B. T., & Spires-Jones, T. L. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0113-1 · Cited by 348 · see citing works
Neuroinflammation in Alzheimer’s Disease
Onyango, I. G., Jauregui, G. V., Čarná, M., Bennett, J. P., & Stokin, G. B. (2021) · Biomedicines · doi:10.3390/biomedicines9050524 · Cited by 330 · see citing works
Going the Extra (Synaptic) Mile: Excitotoxicity as the Road Toward Neurodegenerative Diseases
Armada‐Moreira, A., Gomes, J. I., Pina, C. C., Savchak, O. K., Gonçalves‐Ribeiro, J., Rei, N., Pinto, S., Morais, T. P., Martins, R. S., Ribeiro, F. F., et al. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00090 · Cited by 323 · see citing works
Astrogliosis: An integral player in the pathogenesis of Alzheimer's disease
Osborn, L. M., Kamphuis, W., Wadman, W. J., & Hol, E. M. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.01.001 · Cited by 312 · see citing works
Deciphering the astrocyte reaction in Alzheimer's disease
Perez-Nievas, B. G., & Serrano-Pozo, A. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00114 · Cited by 282 · see citing works
Li, S., & Selkoe, D. J. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15007 · Cited by 264 · see citing works
Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission
Murphy-Royal, C., Dupuis, J. P., Varela, J. A., Panatier, A., Pinson, B., Baufreton, J., Groc, L., & Oliet, S. H. R. (2015) · Nature Neuroscience · doi:10.1038/nn.3901 · Cited by 252 · see citing works
Andersen, J. V., Schousboe, A., & Verkhratsky, A. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102331 · Cited by 259 · see citing works
Astrocyte dysfunction in Alzheimer disease
Acosta, C., Anderson, H. D., & Anderson, C. M. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.24075 · Cited by 248 · see citing works
Targeting Neuroinflammation to Treat Alzheimer’s Disease
Ardura-Fabregat, A., Boddeke, E., Boza‐Serrano, A., Brioschi, S., Castro‐Gomez, S., Ceyzériat, K., Dansokho, C., Dierkes, T., Gelders, G., Heneka, M. T., et al. (2017) · CNS Drugs · doi:10.1007/s40263-017-0483-3 · Cited by 236 · see citing works
GABAergic Inhibitory Interneuron Deficits in Alzheimer’s Disease: Implications for Treatment
Xu, Y., Zhao, M., Han, Y., & Zhang, H. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00660 · Cited by 203 · see citing works
Gąsiorowska, A., Wydrych, M., Drapich, P., Zadrożny, M., Steczkowska, M., Niewiadomski, W., & Niewiadomska, G. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.654931 · Cited by 192 · see citing works
Rossi, D. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.04.003 · Cited by 178 · see citing works
Reactive astrocytes: The nexus of pathological and clinical hallmarks of Alzheimer’s disease
Price, B. R., Johnson, L. A., & Norris, C. M. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101335 · Cited by 173 · see citing works
Current approaches to enhance glutamate transporter function and expression
Fontana, A. C. K. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13200 · Cited by 171 · see citing works
The Role of the Tripartite Glutamatergic Synapse in the Pathophysiology of Alzheimer’s Disease
Rudy, C. C., Hunsberger, H. C., Weitzner, D. S., & Reed, M. N. (2015) · Aging and Disease · doi:10.14336/ad.2014.0423 · Cited by 168 · see citing works
Excitatory Amino Acid Transporters in Physiology and Disorders of the Central Nervous System
Malik, A. R., & Willnow, T. E. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225671 · Cited by 170 · see citing works
The Regulation of Astrocytic Glutamate Transporters in Health and Neurodegenerative Diseases
Todd, A., & Hardingham, G. E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249607 · Cited by 170 · see citing works
Bukke, V. N., Moola, A., Villani, R., Romano, A. D., Wawrzyniak, A., Balawender, K., Orkisz, S., Beggiato, S., Serviddio, G., & Cassano, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207452 · Cited by 160 · see citing works
Role of Vitamin E in the Treatment of Alzheimer’s Disease: Evidence from Animal Models
Gugliandolo, A., Bramanti, P., & Mazzon, E. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122504 · Cited by 167 · see citing works
Zumkehr, J., Rodríguez‐Ortiz, C. J., Cheng, D., Kieu, Z., Wai, T., Hawkins, C., Kilian, J., Lim, S., Medeiros, R., & Kitazawa, M. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.04.005 · Cited by 152 · see citing works
Role of Aβ in Alzheimer’s-related synaptic dysfunction
Zhang, H., Jiang, X., Ma, L., Wei, W., Li, Z., Chang, S., Wen, J., Sun, J., & Li, H. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.964075 · Cited by 144 · see citing works
Blood-brain barrier integrity in the pathogenesis of Alzheimer’s disease
Huang, Z., Wong, L., Su, Y., Huang, X., Wang, N., Chen, H., & Yi, C. (2020) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2020.100857 · Cited by 130 · see citing works
Sompol, P. M., Furman, J. L., Pleiss, M. M., Kraner, S. D., Artiushin, I. A., Batten, S. R., Quintero, J. E., Simmerman, L. A., Beckett, T. L., Lovell, M. A., et al. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.0877-17.2017 · Cited by 121 · see citing works
Avila-Muñoz, E., & Arias, C. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.07.004 · Cited by 114 · see citing works
Ning, J., Huang, S., Chen, S.-D., Zhang, Y.-R., Huang, Y., & Yu, J. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-215411 · Cited by 114 · see citing works
Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders
Satarker, S., Bojja, S. L., Gurram, P. C., Mudgal, J., Arora, D. S., & Nampoothiri, M. (2022) · Cells · doi:10.3390/cells11071139 · Cited by 112 · see citing works
Calcineurin and glial signaling: neuroinflammation and beyond
Furman, J. L., & Norris, C. M. (2014) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0158-7 · Cited by 109 · see citing works
Zádori, D., Veres, G., Szalárdy, L., Klivènyi, P., & Vécsei, L. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170929 · Cited by 107 · see citing works
Bosson, A., Paumier, A., Boisseau, S., Jacquier‐Sarlin, M. R., Buisson, A., & Albrieux, M. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0194-8 · Cited by 104 · see citing works
Miyamoto, T., Stein, L. R., Thomas, R., Djukic, B., Taneja, P., Knox, J. A., Vossel, K. A., & Mucke, L. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0176-x · Cited by 100 · see citing works
Synaptic plasticity in Alzheimer’s disease and healthy aging
Torres, D. M. C., & Cárdenas, F. P. (2020) · Reviews in the Neurosciences · doi:10.1515/revneuro-2019-0058 · Cited by 98 · see citing works
Butterfield, D. A. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101049 · Cited by 97 · see citing works
GLT-1 transporter: An effective pharmacological target for various neurological disorders
Soni, N., Reddy, B. V. K., & Kumar, P. (2014) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2014.10.001 · Cited by 92 · see citing works
Circadian Modulation of Neurons and Astrocytes Controls Synaptic Plasticity in Hippocampal Area CA1
McCauley, J. P., Petroccione, M. A., D’Brant, L. Y., Todd, G. C., Affinnih, N., Wisnoski, J. J., Zahid, S., Shree, S., Sousa, A. A., Guzman, R. M. D., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108255 · Cited by 93 · see citing works
Self-citationRatan, Y., Rajput, A., Maleysm, S., Pareek, A., Jain, V. K., Pareek, A., Kaur, R., & Singh, G. (2023) · Biomedicines · doi:10.3390/biomedicines11051398 · Cited by 87 · see citing works
Arnold, F. J., Putka, A. F., Raychaudhuri, U., Hsu, S., Bedlack, R., Bennett, C. L., & Spada, A. R. L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115587 · Cited by 84 · see citing works
Batarseh, Y. S., & Kaddoumi, A. (2017) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2017.12.006 · Cited by 79 · see citing works
Peterson, A. R., & Binder, D. K. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00164 · Cited by 79 · see citing works
Amyloid-β and Astrocytes Interplay in Amyloid-β Related Disorders
Batarseh, Y. S., Duong, Q.-V., Mousa, Y. M., Rihani, S. B. A., Elfakhri, K. H., & Kaddoumi, A. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17030338 · Cited by 80 · see citing works
Balu, D. T., Pantazopoulos, H., Huang, C. C., Muszynski, K., Harvey, T. L., Uno, Y., Rorabaugh, J. M., Galloway, C. R., Botz-Zapp, C. A., Berretta, S., et al. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104511 · Cited by 77 · see citing works
Brain interference: Revisiting the role of IFNγ in the central nervous system
Monteiro, S., Roque, S., Marques, F., Correia‐Neves, M., & Cerqueira, J. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.05.003 · Cited by 71 · see citing works
Hoshi, A., Tsunoda, A., Yamamoto, T., Tada, M., Kakita, A., & Ugawa, Y. (2018) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12475 · Cited by 70 · see citing works
Succinate dehydrogenase: Prospect for neurodegenerative diseases
Farshbaf, M. J., & Kiani‐Esfahani, A. (2017) · Mitochondrion · doi:10.1016/j.mito.2017.12.002 · Cited by 69 · see citing works
Impairments of glutamatergic synaptic transmission in Alzheimer’s disease
Zott, B., & Konnerth, A. (2022) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2022.03.013 · Cited by 64 · see citing works
Batarseh, Y. S., Mohamed, L. A., Rihani, S. B. A., Mousa, Y. M., Siddique, A. B., Sayed, K. A. E., & Kaddoumi, A. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.03.059 · Cited by 66 · see citing works
Alzheimer's Disease and Sleep–Wake Disturbances: Amyloid, Astrocytes, and Animal Models
Vanderheyden, W. M., Lim, M. M., Musiek, E. S., & Gerstner, J. R. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1135-17.2017 · Cited by 63 · see citing works
Astrocyte and glutamate involvement in the pathogenesis of epilepsy in Alzheimer's disease
Dejakaisaya, H., Kwan, P., & Jones, N. C. (2021) · Epilepsia · doi:10.1111/epi.16918 · Cited by 63 · see citing works
Reactive Astrocytes as Drug Target in Alzheimer’s Disease
Assefa, B. T., Gebre, A. K., & Altaye, B. M. (2018) · BioMed Research International · doi:10.1155/2018/4160247 · Cited by 63 · see citing works
Role of Neuron and Glia in Alzheimer’s Disease and Associated Vascular Dysfunction
Bandyopadhyay, S. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.653334 · Cited by 62 · see citing works
Fan, S., Xian, X., Li, L., Yao, X., Hu, Y., Zhang, M., & Li, W. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180708 · Cited by 61 · see citing works
Kaur, G., Sharma, A., Xu, W., Gerum, S., Alldred, M. J., Subbanna, S., Basavarajappa, B. S., Pawlik, M., Ohno, M., Ginsberg, S. D., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.5338-13.2014 · Cited by 58 · see citing works
Region- and Activity-Dependent Regulation of Extracellular Glutamate
Pinky, N. F., Wilkie, C. M., Barnes, J. R., & Parsons, M. P. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.3213-17.2018 · Cited by 58 · see citing works
Ghosh, S., Durgvanshi, S., Agarwal, S., Raghunath, M., & Sinha, J. K. (2020) · Current Neuropharmacology · doi:10.2174/1570159x18666200429011823 · Cited by 57 · see citing works
Garcia, G., Pinto, S., Ferreira, S., Lopes, D., Serrador, M. J., Fernandes, A., Vaz, A. R., Mendonça, A. D., Edenhofer, F., Malm, T., et al. (2022) · Cells · doi:10.3390/cells11213377 · Cited by 55 · see citing works
“The aberrant accumulation of hypertrophic astrocytes was found around Aβ plaques [11], while Aβ42 was shown to impair the function of the excitatory amino acid transporter (GLT-1) and the glutamate/aspartate transporter (GLAST) in hippocampal astrocytes [12].”
BackgroundActivity-Dependent Plasticity of Astroglial Potassium and Glutamate Clearance
Cheung, G. T. Y., Sibille, J., Zapata, J., & Rouach, N. (2015) · Neural Plasticity · doi:10.1155/2015/109106 · Cited by 54 · see citing works
Karki, P., Smith, K., Johnson, J., Aschner, M., & Lee, E.-S. (2014) · Neurochemistry International · doi:10.1016/j.neuint.2014.08.002 · Cited by 54 · see citing works
Astrocytic glutamatergic transporters are involved in Aβ-induced synaptic dysfunction
Huang, S., Tong, H., Lei, M., Zhou, M., Guo, W., Li, G., Tang, X., Li, Z., Mo, M., Zhang, X., et al. (2017) · Brain Research · doi:10.1016/j.brainres.2017.10.011 · Cited by 52 · see citing works
Synergistic Actions of Microglia and Astrocytes in the Progression of Alzheimer's Disease
Bouvier, D. S., & Murai, K. K. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-143156 · Cited by 51 · see citing works
Regulation of Glutamate, GABA and Dopamine Transporter Uptake, Surface Mobility and Expression
Ryan, R. M., Ingram, S., & Scimemi, A. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.670346 · Cited by 50 · see citing works
Self-citationMembralin deficiency dysregulates astrocytic glutamate homeostasis, leading to ALS-like impairment
Jiang, L.-L., Zhu, B., Zhao, Y., Li, X., Liu, T., Piña-Crespo, J., Zhou, L., Xu, W., Gómez-Rodríguez, M. J., Yu, H., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci127695 · Cited by 49 · see citing works
Hascup, K. N., & Hascup, E. R. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-142160 · Cited by 47 · see citing works
Amyloid Plaques of Alzheimer’s Disease as Hotspots of Glutamatergic Activity
Ovsepian, S. V., O’Leary, V. B., Záborszky, L., Ntziachristos, V., & Dolly, J. O. (2018) · The Neuroscientist · doi:10.1177/1073858418791128 · Cited by 45 · see citing works
Tok, S., Ahnaou, A., & Drinkenburg, W. H. I. M. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210397 · Cited by 44 · see citing works
Brothers, H. M., Bardou, I., Hopp, S. C., Kaercher, R. M., Corona, A. W., Fenn, A. M., Godbout, J. P., & Wenk, G. L. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-013-9476-2 · Cited by 44 · see citing works
Audrain, M., Fol, R. R., Dutar, P., Potier, B., Billard, J., Flament, J., Alves, S., Burlot, M., Dufayet‐Chaffaud, G., Bemelmans, A., et al. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0070-y · Cited by 44 · see citing works
Astrocytes and Adenosine A2A Receptors: Active Players in Alzheimer’s Disease
Lopes, C. R., Cunha, R. A., & Agostinho, P. M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.666710 · Cited by 44 · see citing works
Astrocyte and oligodendrocyte pathology in Alzheimer's disease
Ziar, R., Tesar, P. J., & Clayton, B. L. L. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2025.e00540 · Cited by 47 · see citing works
Tong, H., Zhang, X., Meng, X., Xu, P., Zou, X., & Qu, S. (2017) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2017.01.017 · Cited by 42 · see citing works
Astrocyte in Neurological Disease: Pathogenesis and Therapy
Huang, M., Long, A., Hao, L., Shi, Z., & Zhang, M. (2025) · MedComm · doi:10.1002/mco2.70299 · Cited by 46 · see citing works
Glutamate homeostasis and dopamine signaling: Implications for psychostimulant addiction behavior
Fischer, K. D., Knackstedt, L. A., & Rosenberg, P. A. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104896 · Cited by 40 · see citing works
Fuchsberger, T., Martínez‐Bellver, S., Giraldo, E., Teruel‐Martí, V., Lloret, A., & Viña, J. (2016) · Scientific Reports · doi:10.1038/srep31158 · Cited by 39 · see citing works
Astrocytic microRNAs and transcription factors in Alzheimer’s disease and therapeutic interventions
Nassar, A., Kodi, T., Satarker, S., Chowdari Gurram, P., Upadhya, D., SM, F., Mudgal, J., & Nampoothiri, M. (2022) · Cells · doi:10.3390/cells11244111 · Cited by 36 · see citing works
Astrocytes: The Stars in Neurodegeneration?
Dittlau, K. S., & Freude, K. (2024) · Biomolecules · doi:10.3390/biom14030289 · Cited by 38 · see citing works
Metabotropic glutamate receptors: the potential for therapeutic applications in Alzheimer's disease
Caraci, F., Nicoletti, F., & Copani, A. (2018) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2017.12.001 · Cited by 37 · see citing works
Xu, M., Dong, Y., Wan, S., Yan, T., Cao, J., Wu, L., Bi, K., & Jia, Y. (2016) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.09.018 · Cited by 36 · see citing works
Ristori, S., Bertoni, G., Bientinesi, E., & Monti, D. (2025) · Nutrients · doi:10.3390/nu17111837 · Cited by 41 · see citing works
Tai, C.-H., Bellesi, M., Chen, A.-C., Lin, C.-L., Li, H.-H., Lin, P.-J., Liao, W.-C., Hung, C.-S., Schwarting, R. K., & Ho, Y.-J. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.02.020 · Cited by 34 · see citing works
New Functions of APC/C Ubiquitin Ligase in the Nervous System and Its Role in Alzheimer’s Disease
Fuchsberger, T., Lloret, A., & Viña, J. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18051057 · Cited by 33 · see citing works
Meeker, K. D., Meabon, J. S., & Cook, D. G. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-142304 · Cited by 32 · see citing works
Self-citationControl of complex behavior by astrocytes and microglia
Ortinski, P. I., Reissner, K. J., Turner, J. R., Anderson, T. L., & Scimemi, A. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104651 · Cited by 30 · see citing works
Self-citationCommon Signaling Pathways Involved in Alzheimer’s Disease and Stroke: Two Faces of the Same Coin
Das, T. K., Ganesh, B. P., & Fatima-Shad, K. (2023) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-220108 · Cited by 33 · see citing works
EAAT2 as a therapeutic research target in Alzheimer's disease: A systematic review
Wood, O. W. G., Yeung, J. H. Y., Faull, R. L. M., & Kwakowsky, A. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.952096 · Cited by 29 · see citing works
The complex effects of miR-146a in the pathogenesis of Alzheimer’s disease
Long, Y., Liu, J., Wang, Y., Guo, H.-D., & Cui, G.-H. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-01566 · Cited by 31 · see citing works
Inflammatory Cytokine, IL-1β, Regulates Glial Glutamate Transporter via microRNA-181a in vitro
Zumkehr, J., Rodríguez‐Ortiz, C. J., Medeiros, R., & Kitazawa, M. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170828 · Cited by 28 · see citing works
Puma, D. D. L., Ripoli, C., Puliatti, G., Pastore, F., Lazzarino, G., Tavazzi, B., Arancio, O., Piacentini, R., & Grassi, C. (2022) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12811 · Cited by 28 · see citing works
Glutamate transporter control of ambient glutamate levels
Sun, W., Shchepakin, D., Kalachev, L. V., & Kavanaugh, M. P. (2014) · Neurochemistry International · doi:10.1016/j.neuint.2014.04.007 · Cited by 28 · see citing works
Lan, Y., Zou, S., Chen, J.-J., Zhao, J., & Li, S. (2016) · Neural Plasticity · doi:10.1155/2016/4626593 · Cited by 29 · see citing works
Neuroinflammation and Neurodegeneration
Morales, I., Farias, G. A., Cortés, N., & Maccioni, R. B. (2016) · InTech eBooks · doi:10.5772/64545 · Cited by 28 · see citing works
NMDA receptors in neurodegenerative diseases: mechanisms and emerging therapeutic strategies
Zhang, K., Wen, M., Nan, X., Zhao, S., Li, H., Ai, Y., & Zhu, H. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1604378 · Cited by 27 · see citing works
Recent Insights on Glutamatergic Dysfunction in Alzheimer’s Disease and Therapeutic Implications
Pinky, P. D., Pfitzer, J. C., Senfeld, J. I., Hong, H., Bhattacharya, S., Suppiramaniam, V. D., Qureshi, I., & Reed, M. N. (2022) · The Neuroscientist · doi:10.1177/10738584211069897 · Cited by 26 · see citing works
Aß Pathology and Neuron–Glia Interactions: A Synaptocentric View
Huffels, C. F. M., Middeldorp, J., & Hol, E. M. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03699-6 · Cited by 27 · see citing works
Zoltowska, K. M., Maesako, M., Meier, J. C., & Berezovska, O. (2018) · Scientific Reports · doi:10.1038/s41598-018-26888-2 · Cited by 27 · see citing works
- Authors
- Scimemi, A., Meabon, J. S., Woltjer, R. L., Sullivan, J. M., Diamond, J. S., & Cook, D. G.
- Affiliations
- National Institutes of Health (US)
- VA Puget Sound Health Care System (US)
- Oregon Health & Science University (US)
- University of Washington (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-03-20
- Volume
- 33
- Issue
- 12
- Pages
- 5312-5318
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3866500
- OpenAlex
- W1979889191
- Cited by
- 185
- References
- 28
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 23 · 2023: 9 · 2022: 22 · 2021: 15 · 2020: 18 · 2019: 12 · 2018: 11 · 2017: 19 · 2016: 7 · 2015: 13 · 2014: 11 · 2013: 1
- FWCI
- 7.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (T32AG000258)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK017047)
- National Institute of Neurological Disorders and Stroke (R01NS055804, ZIANS002986, Z01NS002986)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- amyloid-beta 42, GLT-1, glutamate transporters, astrocytes, glutamate clearance, Alzheimer's disease, Trolox, vitamin E, extracellular glutamate
- MeSH terms
- Alzheimer Disease, Animals, Antioxidants, Astrocytes, Chromans, Drug Interactions, Extracellular Space, Female, Hippocampus, Male, Mice, Inbred C57BL, Models, Neurological, Neurons, Organ Culture Techniques, Peptide Fragments, Synapses, Amyloid beta-Peptides, Glutamic Acid, Excitatory Amino Acid Transporter 2, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
