Epilepsy, amyloid-β, and D1 dopamine receptors: a possible pathogenetic link?
Abstract
Experimental and clinical observations indicate that amyloid-β 1-42 (Aβ 1-42) peptide not only represents a major actor in neurodegenerative mechanisms but also induce hyperexcitation in individual neurons and neural circuits. In this abnormal excitability, possibly leading to seizures, the D1 dopamine (DA) receptors may play a role. Cerebrospinal fluid levels of Aβ 1-42 were measured in patients with late-onset epilepsy of unknown etiology. Moreover, the effect of amyloid peptide on the hippocampal epileptic threshold and synaptic plasticity and its link to D1 receptor function were tested in experimental mouse model of cerebral amyloidosis and in acute model of Aβ 1-42-induced neurotoxicity. Among 272 evaluated epileptic patients, aged >55 years, 35 suffered from late-onset epilepsy of unknown etiology. In these subjects, cerebrospinal fluid Aβ 1-42 levels were measured. The effects of Aβ 1-42, amyloid oligomers, and D1 receptor modulation on epileptic threshold were analyzed by electrophysiological recordings in the dentate gyrus of mice hippocampal slices. We found that Aβ 1-42 levels were significantly decreased in cerebrospinal fluid of patients with late-onset epilepsy of unknown etiology with respect to controls suggesting the cerebral deposition of this peptide in these patients. Aβ 1-42 enhanced epileptic activity in mice through a mechanism involving increased surface expression of D1 receptor, and this effect was mimicked by D1 receptor stimulation and blocked by SCH 23390, a D1 receptor antagonist. Aβ 1-42 may contribute to the pathophysiology of late-onset epilepsy of unknown origin. Our preclinical findings indicate that the D1 receptor is involved in mediating the epileptic effects of Aβ 1-42. This novel link between Aβ 1-42 and D1 receptor signaling might represent a potential therapeutic target.
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Multiple studies have established an early link between AD and deficits in mesocorticolimbic DA signalling.
“multiple studies established an early link be tween AD and deficits in mesocorticolimbic DA signalling”
From Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer’s Disease (2021) · cites this paper as Costa et al., 2016
Cites
Berg, A. T., Berkovic, S. F., Brodie, M. J., Buchhalter, J., Cross, J. H., Van Emde Boas, W., Engel, J., French, J., Glauser, T. A., Mathern, G. W., et al. (2010) · Epilepsia · doi:10.1111/j.1528-1167.2010.02522.x · Cited by 4,363 · see citing works
New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory?
Deng, W., Aimone, J. B., & Gage, F. H. (2010) · Nature reviews. Neuroscience · doi:10.1038/nrn2822 · Cited by 2,120 · see citing works
Incidence of Epilepsy and Unprovoked Seizures in Rochester, Minnesota: 1935–1984
Hauser, W. A., Annegers, J. F., & Kurland, L. T. (1993) · Epilepsia · doi:10.1111/j.1528-1157.1993.tb02586.x · Cited by 2,084 · see citing works
Self-propagation of pathogenic protein aggregates in neurodegenerative diseases
Jucker, M., & Walker, L. C. (2013) · Nature · doi:10.1038/nature12481 · Cited by 1,663 · see citing works
Palop, J. J., Chin, J., Roberson, E. D., Wang, J., Thwin, M. T., Bien-Ly, N., Yoo, J., Ho, K. O., Yu, G.-Q., Kreitzer, A., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.07.025 · Cited by 1,653 · see citing works
Amyloid-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 · see citing works
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 · 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
Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice
Chapman, P. F., White, G. L., Jones, M. W., Cooper-Blacketer, D., Marshall, V. J., Irizarry, M., Younkin, L., Good, M. A., Bliss, T. V. P., Hyman, B. T., et al. (1999) · Nature Neuroscience · doi:10.1038/6374 · Cited by 946 · see citing works
Tapiola, T., Alafuzoff, I., Herukka, S.-K., Parkkinen, L., Hartikainen, P., Soininen, H., & Pirttilä, T. (2009) · Archives of Neurology · doi:10.1001/archneurol.2008.596 · Cited by 896 · see citing works
Ras and Rap control AMPA receptor trafficking during synaptic plasticity
Zhu, J. J., Qin, Y., Zhao, M., Van Aelst, L., & Malinow, R. (2002) · Cell · doi:10.1016/s0092-8674(02)00897-8 · Cited by 769 · see citing works
Epilepsy and Cognitive Impairments in Alzheimer Disease
Palop, J. J. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.15 · Cited by 684 · see citing works
Li, S., Jin, M., Koeglsperger, T., Shepardson, N. E., Shankar, G. M., & Selkoe, D. J. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0203-11.2011 · Cited by 664 · see citing works
Amyloid β-Induced Neuronal Hyperexcitability Triggers Progressive Epilepsy
Minkeviciene, R., Rheims, S., Dobszay, M. B., Zilberter, M. Y., Hartikainen, J., Fülöp, L., Penke, B., Zilberter, Y., Harkany, T., Pitkänen, A., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.5215-08.2009 · Cited by 656 · see citing works
Pitkänen, A., & Sutula, T. P. (2002) · The Lancet Neurology · doi:10.1016/s1474-4422(02)00073-x · Cited by 638 · see citing works
CSF Aβ 42 levels correlate with amyloid-neuropathology in a population-based autopsy study
Strozyk, D., Blennow, K., White, L. R., & Launer, L. J. (2003) · Neurology · doi:10.1212/01.wnl.0000046581.81650.d0 · Cited by 604 · see citing works
Incidence and Predictors of Seizures in Patients with Alzheimer's Disease
Amatniek, J. C., Hauser, W. A., del Castillo–Castañeda, C., Jacobs, D. M., Marder, K. S., Bell, K. L., Albert, M., Brandt, J., & Stern, Y. (2006) · Epilepsia · doi:10.1111/j.1528-1167.2006.00554.x · Cited by 592 · see citing works
Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer's disease
D'Amelio, M., Cavallucci, V., Middei, S., Marchetti, C., Pacioni, S., Ferri, A., Diamantini, A., De Zio, D., Carrara, P., Battistini, L., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2709 · Cited by 572 · see citing works
Self-citationPalop, J. J., Jones, B., Kekonius, L., Chin, J., Yu, G.-Q., Raber, J., Masliah, E., & Mucke, L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1133381100 · Cited by 402 · see citing works
Tau Protein Is Required for Amyloid β-Induced Impairment of Hippocampal Long-Term Potentiation
Shipton, O. A., Leitz, J. R., Dworzak, J., Acton, C. E. J., Tunbridge, E. M., Denk, F., Dawson, H. N., Vitek, M. P., Wade-Martins, R., Paulsen, O., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.2610-10.2011 · Cited by 315 · see citing works
Chin, J., Palop, J. J., Puoliväli, J., Massaro, C., Bien-Ly, N., Gerstein, H., Scearce-Levie, K., Masliah, E., & Mucke, L. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2980-05.2005 · Cited by 312 · see citing works
Epileptogenesis in the dentate gyrus: a critical perspective
Dudek, F. E., & Sutula, T. P. (2007) · Progress in brain research · doi:10.1016/s0079-6123(07)63041-6 · Cited by 303 · see citing works
Special considerations in treating the elderly patient with epilepsy
Ramsay, R. E., Rowan, A. J., & Pryor, F. M. (2004) · Neurology · doi:10.1212/wnl.62.5_suppl_2.s24 · Cited by 295 · see citing works
Scarmeas, N., Honig, L. S., Choi, H., Cantero, J., Brandt, J., Blacker, D., Albert, M., Amatniek, J. C., Marder, K. S., Bell, K. L., et al. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.130 · Cited by 293 · see citing works
“Is dopamine involved in Alzheimer's disease?”
Martorana, A., & Koch, G. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00252 · Cited by 276 · see citing works
Patterson, M. A., Szatmari, E. M., & Yasuda, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913875107 · Cited by 259 · see citing works
AMPA receptor trafficking and long-term potentiation
Malinow, R. (2003) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2002.1233 · Cited by 248 · see citing works
Aldenkamp, A. P., & Arends, J. B. A. M. (2003) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2003.11.005 · Cited by 224 · see citing works
Repeated brief seizures induce progressive hippocampal neuron loss and memory deficits
Kotloski, R. J., Lynch, M., Lauersdorf, S., & Sutula, T. P. (2002) · Progress in brain research · doi:10.1016/s0079-6123(02)35010-6 · Cited by 210 · see citing works
Pitkänen, A., Nissinen, J., Nairismägi, J., Łukasiuk, K., Gröhn, O. H. J., Miettinen, R. A., & Kauppinen, R. A. (2002) · Progress in brain research · doi:10.1016/s0079-6123(02)35008-8 · Cited by 202 · see citing works
The role of dopamine signaling in epileptogenesis
Bozzi, Y., & Borrelli, E. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00157 · Cited by 199 · see citing works
Sheng, J. G., Boop, F. A., Mrak, R. E., & Griffin, W. S. T. (1994) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1994.63051872.x · Cited by 198 · see citing works
Ritchie, C. W., Smailagic, N., Noel-Storr, A. H., Takwoingi, Y., Flicker, L. A., Mason, S., & McShane, R. H. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008782.pub4 · Cited by 161 · see citing works
Palop, J. J., Chin, J., Bien‐Ly, N., Massaro, C. M., Yeung, B. Z., Yu, G.-Q., & Mucke, L. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2829-05.2005 · Cited by 144 · see citing works
What is remembered? Role of attention on the encoding and retrieval of hippocampal representations
Muzzio, I. A., Kentros, C. G., & Kandel, E. R. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.172445 · Cited by 136 · see citing works
Epileptic Seizures in AD Patients
Larner, A. J. (2009) · NeuroMolecular Medicine · doi:10.1007/s12017-009-8076-z · Cited by 118 · see citing works
Levodopa ameliorates learning and memory deficits in a murine model of Alzheimer’s disease
Ambrée, O., Richter, H., Sachser, N., Lewejohann, L., Dere, E., de Souza Silva, M. A., Herring, A., Keyvani, K., Paulus, W., & Schäbitz, W.-R. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.11.010 · Cited by 115 · see citing works
Evidence of Aβ‐ and transgene‐dependent defects in ERK‐CREB signaling in Alzheimer’s models
Ma, Q., Harris‐White, M. E., Ubeda, O. J., Simmons, M., Beech, W. K., Lim, G. P., Teter, B., Frautschy, S. A., & Cole, G. M. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04869.x · Cited by 110 · see citing works
Aβ40 Oligomers Identified as a Potential Biomarker for the Diagnosis of Alzheimer's Disease
Gao, C. M., Yam, A. Y., Wang, X., Magdangal, E., Salisbury, C., Peretz, D., Zuckermann, R. N., Connolly, M. D., Hansson, O., Minthon, L., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015725 · Cited by 105 · see citing works
Increased seizure threshold and severity in young transgenic CRND8 mice
Vecchio, R. A. D., Gold, L. H., Novick, S. J., Wong, G., & Hyde, L. A. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.05.107 · Cited by 103 · see citing works
Bicuculline-induced epileptogenesis in the human neocortex maintained in vitro
Hwa, G. G. C., Avoli, M., Oliver, A. P., & Villemure, J. (1991) · Experimental Brain Research · doi:10.1007/bf00231156 · Cited by 88 · see citing works
Jürgensen, S., Antonio, L. L., Mussi, G. E. A., Brito-Moreira, J., Bomfim, T. R., De Felice, F. G., Garrido-Sanabria, E. R., Cavalheiro, É. A., & Ferreira, S. T. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.177790 · Cited by 88 · see citing works
Nigrostriatal Dysfunction in Familial Alzheimer's Disease-Linked APPswe/PS1ΔE9 Transgenic Mice
Perez, S. E., Lazarov, O., Koprich, J. B., Chen, E., Rodriguez‐Menendez, V., Lipton, J. W., Sisodia, S. S., & Mufson, E. J. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2773-05.2005 · Cited by 84 · see citing works
Fà, M., Orozco, I. J., Francis, Y. I., Saeed, F., Gong, Y., & Arancio, O. (2010) · Journal of Visualized Experiments · doi:10.3791/1884 · Cited by 73 · see citing works
Cavallucci, V., Berretta, N., Nobili, A., Nisticò, R., Mercuri, N. B., & D’Amelio, M. (2013) · NeuroMolecular Medicine · doi:10.1007/s12017-013-8241-2 · Cited by 61 · see citing works
Self-citationNisticò, R., Ferraina, C., Marconi, V., Blandini, F., Negri, L., Egebjerg, J., & Feligioni, M. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00063 · Cited by 59 · see citing works
ERK regulation of phosphodiesterase 4 enhances dopamine-stimulated AMPA receptor membrane insertion
Song, R. S., Massenburg, B. B., Wenderski, W., Jayaraman, V., Thompson, L. E., & Neves, S. R. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1311783110 · Cited by 58 · see citing works
Preda, S., Govoni, S. M., Lanni, C., Racchi, M., Mura, E., Grilli, M., & Marchi, M. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301485 · Cited by 49 · see citing works
Trabace, L., Kendrick, K. M., Castrignanò, S., Colaianna, M., Giorgi, A. D., Schiavone, S., Lanni, C., Cuomo, V., & Govoni, S. M. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.04.056 · Cited by 41 · see citing works
Improved Learning and Memory in Aged Mice Deficient in Amyloid β-Degrading Neutral Endopeptidase
Walther, T., Albrecht, D., Becker, M., Schubert, M., Kouznetsova, E., Wiesner, B., Maul, B., Schliebs, R., Grecksch, G., Furkert, J., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004590 · Cited by 40 · see citing works
Expression of β-amyloid precursor protein in refractory epilepsy
Sima, X., Xu, J., Li, J., Zhong, W., & You, C. (2014) · Molecular Medicine Reports · doi:10.3892/mmr.2014.1977 · Cited by 37 · see citing works
Witton, J., Brown, J. T., Jones, M. W., & Randall, A. D. (2010) · Molecular Brain · doi:10.1186/1756-6606-3-32 · Cited by 35 · see citing works
Zhang, J., Wang, C., Deng, T., Xue, Z., Chen, X., Chang, L. Y., & Wang, Q. (2013) · Metabolic Brain Disease · doi:10.1007/s11011-013-9424-0 · Cited by 12 · see citing works
Role of CSF Biomarkers in the Diagnosis of Prodromal Alzheimer‘s Disease
Parnetti, L., & Chiasserini, D. (2011) · Biomarkers in Medicine · doi:10.2217/bmm.11.48 · Cited by 12 · see citing works
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Hansen, J. Y., Shafiei, G., Markello, R. D., Smart, K., Cox, S. M. L., Nørgaard, M., Beliveau, V., Wu, Y., Gallezot, J.-D., Aumont, É., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01186-3 · Cited by 797 · see citing works
Amyloid-β: a potential link between epilepsy and cognitive decline
Romoli, M., Sen, A., Parnetti, L., Calabresi, P., & Costa, C. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00505-9 · Cited by 132 · see citing works
Self-citationAlzheimer's disease and late-onset epilepsy of unknown origin: two faces of beta amyloid pathology
Costa, C., Romoli, M., Liguori, C., Farotti, L., Eusebi, P., Bedetti, C., Siliquini, S., Cesarini, E. N., Romigi, A., Mercuri, N. B., et al. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.09.006 · Cited by 124 · see citing works
Self-citationToxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer
Ngô, H. M., Zhou, Y., Lorenzi, H., Wang, K., Kim, T., Zhou, Y. F., Bissati, K. E., Mui, E. J., Fraczek, L., Rajagopala, S. V., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-10675-6 · Cited by 113 · see citing works
La Barbera, L., Vedele, F., Nobili, A., Krashia, P., Spoleti, E., Latagliata, E. C., Cutuli, D., Cauzzi, E., Marino, R., Viscomi, M. T., et al. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2021.102031 · Cited by 98 · see citing works
“deficits in mesocorticolimbic DA signalling (Allard et al., 1990; Costa et al., 2016; Gibb et al., 1989; Joyce et al., 1997; Kemppainen et al., 2003; Koch et al., 2014; Kumar and Patel, 2007; Murray et al., 1995; Rinne et al., 1986a, 1986b; Storga et al., 1996).”
Self-citationReyes-Marin, K. E., & Nuñez, A. (2017) · Brain Research · doi:10.1016/j.brainres.2017.09.026 · Cited by 84 · see citing works
Hansen, J. Y., Shafiei, G., Markello, R. D., Smart, K. A., Cox, S. M. L., Nørgaard, M., Beliveau, V., Wu, Y., Gallezot, J., Aumont, É., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.28.466336 · Cited by 81 · see citing works
Adult-Onset Epilepsy in Presymptomatic Alzheimer’s Disease: A Retrospective Study
DiFrancesco, J. C., Tremolizzo, L., Polonia, V., Giussani, G., Bianchi, E., Franchi, C., Nobili, A., Appollonio, I. M., Beghi, E., & Ferrarese, C. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170392 · Cited by 81 · see citing works
Self-citationEpilepsy and Alzheimer’s Disease: Potential mechanisms for an association
Giorgi, F. S., Saccaro, L. F., Busceti, C. L., Biagioni, F., & Fornai, F. (2020) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2020.04.009 · Cited by 76 · see citing works
Ren, S., Yao, W., Yan, J.-Z., Jin, C., Yin, J., Yuan, J., Yu, S., & Cheng, Z. (2018) · Scientific Reports · doi:10.1038/s41598-017-18729-5 · Cited by 73 · see citing works
An Unbalanced Synaptic Transmission: Cause or Consequence of the Amyloid Oligomers Neurotoxicity?
Sciaccaluga, M., Megaro, A., Bellomo, G., Ruffolo, G., Romoli, M., Palma, E., & Costa, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115991 · Cited by 70 · see citing works
Self-citationInflammasome-derived cytokine IL18 suppresses amyloid-induced seizures in Alzheimer-prone mice
Tzeng, T.-C., Hasegawa, Y., Iguchi, R., Cheung, A., Caffrey, D. R., Thatcher, E. J., Mao, W., Germain, G., Tamburro, N. D., Okabe, S., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1801802115 · Cited by 67 · see citing works
Alzheimer Disease and Epilepsy
Fang, Y., Si, X., Wang, J., Wang, Z., Chen, Y., Liu, Y., Yan, Y., Tian, J., Zhang, B., & Pu, J. (2023) · Neurology · doi:10.1212/wnl.0000000000207423 · Cited by 66 · see citing works
A review of the mechanisms underlying selected comorbidities in Alzheimer’s disease
Maciejewska, K., Czarnecka, K., & Szymański, P. (2021) · Pharmacological Reports · doi:10.1007/s43440-021-00293-5 · Cited by 64 · see citing works
Kaestner, E. J., Reyes, A., Chen, A., Rao, J., Macari, A. C., Choi, J. Y., Qiu, D., Hewitt, K. C., Wang, Z. I., Drane, D. L., et al. (2020) · Brain · doi:10.1093/brain/awaa397 · Cited by 61 · see citing works
Neurodegenerative pathways as targets for acquired epilepsy therapy development
Casillas-Espinosa, P. M., Ali, I. Y., & O'Brien, T. J. (2020) · Epilepsia Open · doi:10.1002/epi4.12386 · Cited by 58 · see citing works
Tombini, M., Assenza, G., Ricci, L., Lanzone, J., Boscarino, M., Vico, C., Magliozzi, A., & Lazzaro, V. D. (2021) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-200286 · Cited by 54 · see citing works
Outcome of childhood-onset epilepsy from adolescence to adulthood: Transition issues
Nabbout, R., Andrade, D. M., Bahi‐Buisson, N., Cross, J. H., Desquerre, I., Dulac, O., Granata, T., Hirsch, É., Navarro, V., Ouss, L., et al. (2017) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2016.11.010 · Cited by 53 · see citing works
Cesarini, E. N., Babiloni, C., Salvadori, N., Farotti, L., Percio, C. D., Pascarelli, M. T., Noce, G., Lizio, R., Re, F. D., Isella, V., et al. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00199 · Cited by 47 · see citing works
Self-citationPore-Forming Proteins as Mediators of Novel Epigenetic Mechanism of Epilepsy
Surguchov, A. P., Surgucheva, I. G., Sharma, M., Sharma, R. A., & Singh, V. (2017) · Frontiers in Neurology · doi:10.3389/fneur.2017.00003 · Cited by 47 · see citing works
Li, H., Yang, P., Knight, W. C., Guo, Y., Perlmutter, J. S., Benzinger, T. L. S., Morris, J. C., & Xu, J. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14898 · Cited by 45 · see citing works
Zhang, X., & Zheng, J. (2019) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2019.04.040 · Cited by 41 · see citing works
The Role of Neuroinflammation in Post-traumatic Epilepsy
Sun, L., Wei, S., Yang, H.-J., Liu, R., Wu, J.-P., & Wang, Q. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.646152 · Cited by 35 · see citing works
Perversi, F., Costa, C., Labate, A., Lattanzi, S., Liguori, C., Maschio, M. C. E., Meletti, S., Nobili, L., Operto, F. F., Romigi, A., et al. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1182304 · Cited by 39 · see citing works
Self-citationLate-onset unexplained epilepsy: What are we missing?
Sarkis, R. A., Willment, K., Pennell, P. B., & Marshall, G. A. (2019) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2019.106478 · Cited by 39 · see citing works
Mechanisms Involved in Epileptogenesis in Alzheimer’s Disease and Their Therapeutic Implications
Altuna, M., Olmedo‐Saura, G., Carmona‐Iragui, M., & Fortea, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084307 · Cited by 39 · see citing works
Targeting neurodegeneration to prevent post-traumatic epilepsy.
Ali, I., Silva, J. C., Liu, S., Shultz, S. R., Kwan, P., Jones, N. C., & O'Brien, T. J. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.08.006 · Cited by 38 · see citing works
Hickman, L. B., Stern, J. M., Silverman, D. H. S., Salamon, N., & Vossel, K. A. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1241638 · Cited by 36 · see citing works
Salgado-Puga, K., Rodríguez-Colorado, J., Prado-Alcalá, R. A., & Peña‐Ortega, F. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-160543 · Cited by 35 · see citing works
New anti-seizure medication for elderly epilepsy patients - a critical narrative review
Rohracher, A., Kalss, G., Kuchukhidze, G., Neuray, C., Leitinger, M., Höfler, J., Kreidenhuber, R., Rossini, F., Volna, K., Mauritz, M., et al. (2020) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2020.1843636 · Cited by 36 · see citing works
Fernandes, M., Manfredi, N., Aluisantonio, L., Franchini, F., Chiaravalloti, A., Izzi, F., Santo, S. G. D., Schillaci, O., Mercuri, N. B., Placidi, F., et al. (2022) · European Journal of Neuroscience · doi:10.1111/ejn.15734 · Cited by 35 · see citing works
Self-citationIncidence of dementia in patients with adult-onset epilepsy of unknown causes
Kawakami, O., Koike, Y., Ando, T., Sugiura, M., Kato, H., Hiraga, K., Kito, H., & KONDO, H. (2018) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2018.09.010 · Cited by 34 · see citing works
Liguori, C., Costa, C., Franchini, F., Izzi, F., Spanetta, M., Cesarini, E. N., Santo, S. G. D., Manfredi, N., Farotti, L., Romoli, M., et al. (2019) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2019.106592 · Cited by 35 · see citing works
Self-citationMao, R., Hu, M., Liu, X., Ye, L., Xu, B., Sun, M., Xu, S., Shao, W., Tan, Y. J., Xu, Y., et al. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01528-7 · Cited by 30 · see citing works
On the relationships between epilepsy, sleep, and Alzheimer’s disease: A narrative review
Hanke, J.-M., Schindler, K. A., & Seiler, A. (2022) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2022.108609 · Cited by 27 · see citing works
Late-onset temporal lobe epilepsy: insights from brain atrophy and Alzheimer’s disease biomarkers
Ballerini, A., Biagioli, N., Carbone, C., Chiari, A., Tondelli, M., Vinceti, G., Bedin, R., Malagoli, M., Genovese, M., Scolastico, S., et al. (2024) · Brain · doi:10.1093/brain/awae207 · Cited by 24 · see citing works
Alcantara‐Gonzalez, D., Villasana‐Salazar, B., & Peña‐Ortega, F. (2019) · Hippocampus · doi:10.1002/hipo.23129 · Cited by 23 · see citing works
Late-onset epilepsy clinic: From clinical diagnostics to biomarkers
Punia, V., Bhansali, S., & Tsai, C. (2024) · Seizure · doi:10.1016/j.seizure.2024.06.026 · Cited by 23 · see citing works
Montelukast: The New Therapeutic Option for the Treatment of Epilepsy
Tesfaye, B. A., Hailu, H. G., Zewdie, K. A., Ayza, M. A., & Berhe, D. F. (2021) · Journal of Experimental Pharmacology · doi:10.2147/jep.s277720 · Cited by 23 · see citing works
Antiseizure Medications in Alzheimer’s Disease from Preclinical to Clinical Evidence
Bosco, F., Guarnieri, L., Rania, V., Palma, E., Citraro, R., Corasaniti, M. T., Leo, A., & Sarro, G. D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241612639 · Cited by 22 · see citing works
CSF biomarkers in patients with epilepsy in Alzheimer’s disease: a nation-wide study
Banote, R. K., Håkansson, S., Zetterberg, H., & Zelano, J. (2022) · Brain Communications · doi:10.1093/braincomms/fcac210 · Cited by 22 · see citing works
Bioinformatic analysis identifies potential key genes of epilepsy
Zhu, Y., Huang, D., Zhao, Z., & Lu, C. (2021) · PLoS ONE · doi:10.1371/journal.pone.0254326 · Cited by 20 · see citing works
Sleep: The Tip of the Iceberg in the Bidirectional Link Between Alzheimer's Disease and Epilepsy
Szabo, A. B., Cretin, B., Gérard, F., Curot, J., Barbeau, E. J., Pariente, J., Dahan, L., & Valton, L. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.836292 · Cited by 19 · see citing works
Temporal lobe dysfunction in late-onset epilepsy of unknown origin
DiFrancesco, J. C., Isella, V., Licciardo, D., Crivellaro, C., Musarra, M., Guerra, L., Salvadori, N., Chipi, E., Calvello, C., Costa, C., et al. (2021) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2021.107839 · Cited by 18 · see citing works
Self-citationXu, X., Mei, B., Yang, Y., Li, J., Weng, J., Yang, Y., Zhu, Q., Zhang, H., & Liu, X. (2025) · International Journal of Biological Sciences · doi:10.7150/ijbs.109315 · Cited by 17 · see citing works
Clinical and Instrumental Characterization of Patients With Late-Onset Epilepsy
DiFrancesco, J. C., Labate, A., Romoli, M., Chipi, E., Salvadori, N., Galimberti, C. A., Perani, D., Ferrarese, C., & Costa, C. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.851897 · Cited by 17 · see citing works
Self-citationBellingacci, L., Tallarico, M., Mancini, A., Megaro, A., Caro, C. D., Citraro, R., Sarro, G. D., Tozzi, A., Filippo, M. D., Sciaccaluga, M., et al. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109373 · Cited by 17 · see citing works
Self-citationLate onset epilepsy and Alzheimer’s disease: exploring the dual pathogenic role of amyloid-β
Costa, C., Romoli, M., & Calabresi, P. (2018) · Brain · doi:10.1093/brain/awy162 · Cited by 17 · see citing works
Self-citationGene therapy for Lafora disease in the Epm2a mouse model
Zafra‐Puerta, L., Iglesias‐Cabeza, N., Burgos, D. F., Sciaccaluga, M., González‐Fernández, J., Bellingacci, L., Canonichesi, J., Sánchez‐Martín, G., Costa, C., Sánchez, M. P., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.05.032 · Cited by 17 · see citing works
Self-citationSuzuki, Y. (2019) · Sensors · doi:10.3390/s19183928 · Cited by 16 · see citing works
Liguori, C., Spanetta, M., Romoli, M., Placidi, F., Cesarini, E. N., Mercuri, N. B., & Costa, C. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111434 · Cited by 16 · see citing works
Self-citationZhou, J., Peng, C. Y., Li, Q., Yan, X., Yang, L., Li, M., Cao, X., Xie, X., Chen, D., Rao, C., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.837810 · Cited by 15 · see citing works
Tzavellas, N. P., Tsamis, K. I., Katsenos, A. P., Davri, A. S., Simos, Y. V., Nikas, I. P., Bellos, S., Lekkas, P., Kanellos, F. S., Konitsiotis, S., et al. (2024) · Cells · doi:10.3390/cells13050434 · Cited by 14 · see citing works
Costa, C., Vecchio, F., Romoli, M., Miraglia, F., Cesarini, E. N., Alù, F., Calabresi, P., & Rossini, P. M. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210350 · Cited by 13 · see citing works
Self-citationExploring biomarkers of neurodegeneration in epilepsy: Critical insights
Farhan, R., Hashmi, S. A., Kapur, J., D’Abreu, A., Punia, V., Manning, C. A., Smith, V. L., & Zawar, I. (2025) · Epileptic Disorders · doi:10.1002/epd2.70023 · Cited by 13 · see citing works
A Dual Effect of Dopamine on Hippocampal LTP and Cognitive Functions in Control and Kindled Mice
Ahmadi, M., Rouhi, N., Fathollahi, Y., Shojaei, A., Rezaei, M., Rostami, S., Saab, B. J., & Mirnajafi‐Zadeh, J. (2023) · Journal of Neuroscience · doi:10.1523/jneurosci.0926-21.2023 · Cited by 11 · see citing works
Antiepileptic Drugs as Potential Dementia Prophylactics Following Traumatic Brain Injury
Locskai, L. F., Alyenbaawi, H., & Allison, W. T. (2023) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-051921-013930 · Cited by 11 · see citing works
Datta, S., Kanjilal, B., & Sarkar, P. (2018) · Journal of Environmental Science and Health Part A · doi:10.1080/10934529.2018.1474574 · Cited by 11 · see citing works
Citraro, R., Leo, A., Tallarico, M., Sciaccaluga, M., & Costa, C. (2022) · Current Neuropharmacology · doi:10.2174/1570159x20666220507020635 · Cited by 12 · see citing works
Self-citationBurgos, D. F., Sciaccaluga, M., Worby, C. A., Zafra‐Puerta, L., Iglesias‐Cabeza, N., Sánchez‐Martín, G., Prontera, P., Costa, C., Serratosa, J. M., & Sánchez, M. P. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106119 · Cited by 10 · see citing works
Self-citationCD36 Deficiency Suppresses Epileptic Seizures
Zheng, F., Yang, Y., Lu, S., Yang, Q. Z., Li, Y., Xu, X., Zhang, Y., Liu, F., Tian, X., & Wang, X. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.10.024 · Cited by 10 · see citing works
Monoamines and their Derivatives on GPCRs: Potential Therapy for Alzheimer’s Disease
Farfán‐García, E. D., Márquez-Gómez, R., Barrón‐González, M., Pérez‐Capistran, T., Rosales‐Hernández, M. C., Pinto‐Almazán, R., & Soriano-Ursua, M. A. (2019) · Current Alzheimer Research · doi:10.2174/1570159x17666190409144558 · Cited by 10 · see citing works
Lehmann, L. M., & Barker‐Haliski, M. L. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1223472 · Cited by 6 · see citing works
Protein profiling and assessment of amyloid beta levels in plasma in canine refractory epilepsy
Phochantachinda, S., Chantong, B., Reamtong, O., & Chatchaisak, D. (2023) · Frontiers in Veterinary Science · doi:10.3389/fvets.2023.1258244 · Cited by 7 · see citing works
Bellingacci, L., Canonichesi, J., Sciaccaluga, M., Megaro, A., Mazzocchetti, P., Mauro, M. D., Costa, C., Filippo, M. D., Pettorossi, V. E., & Tozzi, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031377 · Cited by 7 · see citing works
Self-citationEffect of late-onset epilepsy on cognitive functioning in patients with small vessel disease
Turón, M., Jiménez-Baladó, J., Abraira, L., Fonseca, E., Quintana, M., Toledo, M., Delgado, P., Maisterra, O., Salas‐Puig, X., Álvarez‐Sabín, J., et al. (2021) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2021.108238 · Cited by 7 · see citing works
Zafra‐Puerta, L., Iglesias‐Cabeza, N., Sciaccaluga, M., Bellingacci, L., Canonichesi, J., Sánchez‐Martín, G., Costa, C., Sánchez, M. P., & Serratosa, J. M. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70514 · Cited by 6 · see citing works
Self-citationElectrophysiological insights into Alzheimer's disease: A review of human and animal studies
Calvin, K., McNeela, A. M., Osse, A. M. L., Bhasin, G., Ridenour, M., Kinney, J. W., & Hyman, J. M. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105987 · Cited by 6 · see citing works
Maio, S., Fernandes, M., Placidi, F., Izzi, F., Castelli, A., Pagano, A., Mercuri, N. B., & Liguori, C. (2025) · Epilepsy Research · doi:10.1016/j.eplepsyres.2025.107614 · Cited by 5 · see citing works
Self-citationSciaccaluga, M., Ruffolo, G., Palma, E., & Costa, C. (2023) · Current Neuropharmacology · doi:10.2174/1570159x21666230504160948 · Cited by 7 · see citing works
Self-citationVyver, M. V., Daeninck, L., Smet, G. D., Aourz, N., Sahu, S., Engelborghs, S., Pauwels, K., Bundel, D. D., & Smolders, I. J. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1239140 · Cited by 4 · see citing works
Oveisgharan, S., Grodstein, F., Evia, A. M., James, B. D., Capuano, A. W., Chen, Y., Arfanakis, K., Schneider, J. A., & Bennett, D. A. (2024) · Neurology · doi:10.1212/wnl.0000000000209172 · Cited by 4 · see citing works
Anastassopoulou, J., Kyriakidou, M., Nisianakis, P., Papatheodorou, G. N., Rallis, M. C., & Theophanides, T. (2019) · Journal of Basic & Applied Sciences · doi:10.29169/1927-5129.2019.15.07 · Cited by 4 · see citing works
Temporal Lobe Cavernous Malformation Caused Epileptic Amnesic Episodes and Mild Cognitive Impairment
Hirokawa, Y., Fujimoto, A., Ichikawa, N., Sato, K., Tanaka, T., Enoki, H., Otsuki, Y., & Okanishi, T. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00620 · Cited by 3 · see citing works
Reply: Late onset epilepsy and Alzheimer’s disease: exploring the dual pathogenic role of amyloid-β
Sen, A., & Masud Husain, B. (2018) · Brain · doi:10.1093/brain/awy163 · Cited by 3 · see citing works
Hickman, L. B., Pandey, B., Fish, A., Bandla, M., Husein, A., Allas, C. H., Kottakota, H., Herzog, L., Vossel, K. A., & Stern, J. M. (2025) · Epilepsia Open · doi:10.1002/epi4.70156 · Cited by 2 · see citing works
Epileptogenesis in Posttraumatic Epilepsy
Ngadimon, I. W., Zulazmi, N. A., & Shaikh, M. F. (2023) · Springer eBooks · doi:10.1007/978-981-19-3949-5_20-1 · Cited by 1 · see citing works
Szabo, A. B., Sayegh, F. J. P., Gauzin, S., Lejards, C., Guiard, B. P., Valton, L., Verret, L., Rampon, C., & Dahan, L. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16268 · Cited by 2 · see citing works
Kuzuya, A., Ohara, T., & Akamatsu, N. (2025) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2025.2581758 · Cited by 1 · see citing works
Late-onset epilepsy as a prodromal symptom
Dupont, S. (2025) · Revue Neurologique · doi:10.1016/j.neurol.2025.07.007 · Cited by 1 · see citing works
Neuronal hyperexcitability: A key to unraveling hippocampal synaptic dysfunction in Lafora disease
Costa, C., Bellingacci, L., Canonichesi, J., Imperatore, V., Taddei, A. A., Zafra‐Puerta, L., Iglesias‐Cabeza, N., Prontera, P., Mancini, A., Filippo, M. D., et al. (2025) · Epilepsia · doi:10.1111/epi.70024 · Cited by 1 · see citing works
Self-citationFrom comorbidity to continuum: Alzheimer’s disease and epilepsy are connected-now what?
Alves, S. S., Manzine, P. R., dos Santos, F. M., Migliaccio, M. M., Alves, L. D. C., da Silva-Júnior, R. M. P., Becerra-Hernández, L. V., González-Acosta, C. A., Buriticá, E., Cominetti, M. R., et al. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106682 · Cited by 1 · see citing works
Fratto, E., Buonocore, J., Fortunato, F., Sammarra, I., Calomino, C., Vescio, B., Quattrone, A., Gambardella, A., & Quattrone, A. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261450962 · Cited by 1 · see citing works
Histopathological Evidence of Neurodegenerative Pathology in Epilepsy: A Systematic Review
Hashmi, S. A., Łuniewski, A., Smith, V. L., McCord, M., Kapur, J., Quigg, M., Joshua, C., & Zawar, I. (2026) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.70486 · Cited by 1 · see citing works
Romigi, A., Costa, C., Sen, A., & Giorgi, F. S. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.1063299
Self-citationEpilepsy and Neurodegeneration
Retinasamy, T., & Shaikh, M. F. (2023) · Springer eBooks · doi:10.1007/978-981-19-3949-5_23-1
D’Amelio, M., & Costa, C. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16359
Self-citationEpileptogenesis in Posttraumatic Epilepsy
Ngadimon, I. W., Zulazmi, N. A., & Shaikh, M. F. (2024) · Springer eBooks · doi:10.1007/978-981-99-7557-0_20
Epilepsy and Neurodegeneration
Retinasamy, T., & Shaikh, M. F. (2024) · Springer eBooks · doi:10.1007/978-981-99-7557-0_23
Cesarini, E. N., Falcicchio, G., Librizzi, L., Sciaccaluga, M., Assenza, G., Galimberti, C. A., Giorgi, F. S., DiFrancesco, J. C., Costa, C., & the “Late‐Onset Epilepsy Study Group” of the Lega Italiana contro l'Epilessia (LICE), T. I. C. O. T. I. L. A. E. (. (2025) · Epilepsia Open · doi:10.1002/epi4.70131
Self-citationMajou, D., & Dermenghem, A.-L. (2025) · OCL · doi:10.1051/ocl/2025032
Sleep disturbances are common in late‐onset epilepsy of unknown origin
Maio, S., Fernandes, M., Costa, C., Bergamo, G., Dono, F., Santo, S. G. D., Silla, M., Ricci, A., Quintieri, P., Franchini, F., et al. (2026) · Epileptic Disorders · doi:10.1002/epd2.70194
Self-citationWan, H., Chen, Y., Zhang, X., Yu, Z., Zheng, K.-M., Shao, X., Bi, M., Jiang, B., & (775482), Z. W. (2026) · Neurobiology of Disease · doi:10.1016/j.nbd.2026.107483
Wada, T., Kuzuya, A., Koda, K., Ueda, S., Shima, A., Sawamoto, N., Ikeda, A., Takahashi, R., & Matsumoto, R. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1807027
- Authors
- Costa, C., Parnetti, L., D'Amelio, M., Tozzi, A., Tantucci, M., Romigi, A., Siliquini, S., Cavallucci, V., Di Filippo, M., Mazzocchetti, P., Liguori, C., Nobili, A., Eusebi, P., Mercuri, N. B., & Calabresi, P.
- Affiliations
- University of Perugia (IT)
- University of Rome Tor Vergata (IT)
- Fondazione Santa Lucia (IT)
- Università Campus Bio-Medico (IT)
- Corresponding author
- Costa, Cinzia
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 48
- Pages
- 161-171
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2517151712
- Cited by
- 94
- References
- 54
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 12 · 2023: 13 · 2022: 11 · 2021: 13 · 2020: 5 · 2019: 9 · 2018: 8 · 2017: 7
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Funders
- Progetto di Ricerca di Interesse Nazionale
- Progetti del Ministero della Salute (GR-2010-2315007)
- Minister of Health (GR-2011-02351457)
- Alzheimer's Association, United States (NIRG-11-204588)
- Cassa di Risparmio di Perugia ((2014.0258.021))
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- amyloid-beta 42, dopamine D1 receptor, late-onset epilepsy, cerebrospinal fluid amyloid-beta, cerebral amyloidosis, dentate gyrus, synaptic plasticity, amyloid oligomers, neurotoxicity, SCH 23390, therapeutic target
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Animals, Benzazepines, Disease Models, Animal, Epilepsy, Female, Humans, Male, Mice, Transgenic, Middle Aged, Peptide Fragments, Amyloid beta-Peptides, Receptors, Dopamine D1
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