{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:42:56Z","timestamp":1792010576137,"version":"4.4.0"},"reference-count":116,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T00:00:00Z","timestamp":1658102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Tau is a microtubule-associated protein known to bind and promote assembly of microtubules in neurons under physiological conditions. However, under pathological conditions, aggregation of hyperphosphorylated tau causes neuronal toxicity, neurodegeneration, and resulting tauopathies like Alzheimer\u2019s disease (AD). Clinically, patients with tauopathies present with either dementia, movement disorders, or a combination of both. The deposition of hyperphosphorylated tau in the brain is also associated with epilepsy and network hyperexcitability in a variety of neurological diseases. Furthermore, pharmacological and genetic targeting of tau-based mechanisms can have anti-seizure effects. Suppressing tau phosphorylation decreases seizure activity in acquired epilepsy models while reducing or ablating tau attenuates network hyperexcitability in both Alzheimer\u2019s and epilepsy models. However, it remains unclear whether tauopathy and epilepsy comorbidities are mediated by convergent mechanisms occurring upstream of epileptogenesis and tau aggregation, by feedforward mechanisms between the two, or simply by coincident processes. In this review, we investigate the relationship between tauopathies and seizure disorders, including temporal lobe epilepsy (TLE), post-traumatic epilepsy (PTE), autism spectrum disorder (ASD), Dravet syndrome, Nodding syndrome, Niemann-Pick type C disease (NPC), Lafora disease, focal cortical dysplasia, and tuberous sclerosis complex. We also explore potential mechanisms implicating the role of tau kinases and phosphatases as well as the mammalian target of rapamycin (mTOR) in the promotion of co-pathology. Understanding the role of these co-pathologies could lead to new insights and therapies targeting both epileptogenic mechanisms and cognitive decline.<\/jats:p>","DOI":"10.3389\/fnagi.2022.903973","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T06:47:36Z","timestamp":1658126856000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":38,"title":["Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms"],"prefix":"10.3389","volume":"14","author":[{"given":"Kaylin","family":"Hwang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahil N.","family":"Vaknalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwaku","family":"Addo-Osafo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariane","family":"Vicente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Vossel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.nbd.2018.08.006","article-title":"Targeting neurodegeneration to prevent post-traumatic epilepsy.","volume":"123","author":"Ali","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2019.00308","article-title":"Tau phosphorylation in a mouse model of temporal lobe epilepsy.","volume":"11","author":"Alves","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.58744","article-title":"Seizures are a druggable mechanistic link between TBI and subsequent tauopathy.","volume":"10","author":"Alyenbaawi","year":"2021","journal-title":"eLife"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.5006","article-title":"Dravet syndrome: an overview.","volume":"11","author":"Anwar","year":"2019","journal-title":"Cureus"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1992","DOI":"10.1021\/acschemneuro.8b00281","article-title":"Identification of GSK-3 as a potential therapeutic entry point for epilepsy.","volume":"10","author":"Aourz","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1212\/WNL.0b013e31827f0fd1","article-title":"Criteria for the diagnosis of corticobasal degeneration.","volume":"80","author":"Armstrong","year":"2013","journal-title":"Neurology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1016\/j.wneu.2016.12.074","article-title":"Prevalence and incidence of drug-resistant mesial temporal lobe epilepsy in the United States.","volume":"99","author":"Asadi-Pooya","year":"2017","journal-title":"World Neurosurg."},{"key":"B8","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1007\/BF00318566","article-title":"Paired helical filament tau (PHFtau) in Niemann-Pick type C disease is similar to PHFtau in Alzheimer\u2019s disease.","volume":"90","author":"Auer","year":"1995","journal-title":"Acta Neuropathol."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2021.136096","article-title":"Differential regulation of excitatory synaptic transmission in the hippocampus and anterior temporal lobe by cyclin dependent kinase 5 (Cdk5) in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS).","volume":"761","author":"Banerjee","year":"2021","journal-title":"Neurosci. Lett."},{"key":"B10","doi-asserted-by":"publisher","first-page":"211","DOI":"10.3233\/JAD-170031","article-title":"Relative incidence of seizures and myoclonus in Alzheimer\u2019s disease, dementia with lewy bodies, and frontotemporal dementia.","volume":"60","author":"Beagle","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.conb.2009.06.003","article-title":"A synaptic trek to autism.","volume":"19","author":"Bourgeron","year":"2009","journal-title":"Curr. Opin. Neurobiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1097\/NEN.0b013e318232a379","article-title":"Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years.","volume":"70","author":"Braak","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B13","doi-asserted-by":"crossref","first-page":"6515","DOI":"10.1523\/JNEUROSCI.22-15-06515.2002","article-title":"Deregulation of cdk5, hyperphosphorylation, and cytoskeletal pathology in the Niemann-Pick type C murine model.","volume":"22","author":"Bu","year":"2002","journal-title":"J. Neurosci."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2015.00163","article-title":"Effects of rapamycin treatment on neurogenesis and synaptic reorganization in the dentate gyrus after controlled cortical impact injury in mice.","volume":"9","author":"Butler","year":"2015","journal-title":"Front. Syst. Neurosci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1111\/acel.12057","article-title":"mTOR regulates tau phosphorylation and degradation: implications for Alzheimer\u2019s disease and other tauopathies.","volume":"12","author":"Caccamo","year":"2013","journal-title":"Aging Cell"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1113\/jphysiol.2010.187484","article-title":"NaV1.1 channels and epilepsy.","volume":"588","author":"Catterall","year":"2010","journal-title":"J. Physiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/s0896-6273(01)80044-1","article-title":"Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality.","volume":"18","author":"Chae","year":"1997","journal-title":"Neuron"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109855","article-title":"Tau reduction affects excitatory and inhibitory neurons differently, reduces excitation\/inhibition ratios, and counteracts network hypersynchrony.","volume":"37","author":"Chang","year":"2021","journal-title":"Cell Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"8965","DOI":"10.1523\/JNEUROSCI.20-24-08965.2000","article-title":"Induction of cyclin-dependent kinase 5 in the hippocampus by chronic electroconvulsive seizures: role of [Delta]FosB.","volume":"20","author":"Chen","year":"2000","journal-title":"J. Neurosci."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2013.00122","article-title":"Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease.","volume":"4","author":"Chesser","year":"2013","journal-title":"Front. Neurol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.1111\/epi.16589","article-title":"Zebrafish model of posttraumatic epilepsy.","volume":"61","author":"Cho","year":"2020","journal-title":"Epilepsia"},{"key":"B22","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1007\/s00401-014-1349-0","article-title":"Primary age-related tauopathy (PART): a common pathology associated with human aging.","volume":"128","author":"Crary","year":"2014","journal-title":"Acta Neuropathol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/s0896-6273(03)00627-5","article-title":"Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles.","volume":"40","author":"Cruz","year":"2003","journal-title":"Neuron"},{"key":"B24","doi-asserted-by":"publisher","first-page":"12887","DOI":"10.1523\/JNEUROSCI.2107-13.2013","article-title":"Antisense reduction of tau in adult mice protects against seizures.","volume":"33","author":"DeVos","year":"2013","journal-title":"J. Neurosci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1111\/epi.13345","article-title":"Effects of rapamycin and curcumin treatment on the development of epilepsy after electrically induced status epilepticus in rats.","volume":"57","author":"Drion","year":"2016","journal-title":"Epilepsia"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1111\/j.1471-4159.2006.04139.x","article-title":"Chronic lithium administration to FTDP-17 tau and GSK-3beta overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but pre-formed neurofibrillary tangles do not revert.","volume":"99","author":"Engel","year":"2006","journal-title":"J. Neurochem."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1093\/hmg\/11.11.1251","article-title":"Targeted disruption of the Epm2a gene causes formation of Lafora inclusion bodies, neurodegeneration, ataxia, myoclonus epilepsy and impaired behavioral response in mice.","volume":"11","author":"Ganesh","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"B28","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.nbd.2013.06.005","article-title":"Hyperexcitability and epileptic seizures in a model of frontotemporal dementia.","volume":"58","author":"Garcia-Cabrero","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22063209","article-title":"Alterations in tau protein level and phosphorylation state in the brain of the autistic-like rats induced by prenatal exposure to valproic acid.","volume":"22","author":"Gassowska-Dobrowolska","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1002\/ana.24230","article-title":"Tau reduction prevents disease in a mouse model of Dravet syndrome.","volume":"76","author":"Gheyara","year":"2014","journal-title":"Ann. Neurol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1093\/brain\/awz381","article-title":"Alzheimer-like amyloid and tau alterations associated with cognitive deficit in temporal lobe epilepsy.","volume":"143","author":"Gourmaud","year":"2020","journal-title":"Brain"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064078","article-title":"Rapamycin attenuates the development of posttraumatic epilepsy in a mouse model of traumatic brain injury.","volume":"8","author":"Guo","year":"2013","journal-title":"PLoS One"},{"key":"B33","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/j.braindev.2006.12.012","article-title":"Autism and epilepsy: a retrospective follow-up study.","volume":"29","author":"Hara","year":"2007","journal-title":"Brain Dev."},{"key":"B34","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1146\/annurev-pathol-012615-044116","article-title":"Chronic traumatic encephalopathy: the neuropathological legacy of traumatic brain injury.","volume":"11","author":"Hay","year":"2016","journal-title":"Annu. Rev. Pathol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1684\/epd.2015.0739","article-title":"Cognitive impairment in epilepsy: the role of network abnormalities.","volume":"17","author":"Holmes","year":"2015","journal-title":"Epileptic Disord."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1523\/JNEUROSCI.3191-12.2013","article-title":"Tau loss attenuates neuronal network hyperexcitability in mouse and Drosophila genetic models of epilepsy.","volume":"33","author":"Holth","year":"2013","journal-title":"J. Neurosci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1016\/j.clinph.2021.03.050","article-title":"Subclinical epileptiform activity accelerates the progression of Alzheimer\u2019s disease: a long-term EEG study.","volume":"132","author":"Horvath","year":"2021","journal-title":"Clin. Neurophysiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1093\/jnen\/nlz090","article-title":"Neuroinflammation and not tauopathy is a predominant pathological signature of nodding syndrome.","volume":"78","author":"Hotterbeekx","year":"2019","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.nbd.2010.05.024","article-title":"Pharmacological inhibition of the mammalian target of rapamycin pathway suppresses acquired epilepsy.","volume":"40","author":"Huang","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"B40","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.cell.2010.06.036","article-title":"Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer\u2019s disease mouse models.","volume":"142","author":"Ittner","year":"2010","journal-title":"Cell"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/bpa.12060","article-title":"Cell injury and premature neurodegeneration in focal malformations of cortical development.","volume":"24","author":"Iyer","year":"2014","journal-title":"Brain Pathol."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2020.118745","article-title":"Control of neuronal excitability by GSK-3beta: epilepsy and beyond.","volume":"1867","author":"Jaworski","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/j.1750-3639.2011.00513.x","article-title":"Widespread tau and amyloid-beta pathology many years after a single traumatic brain injury in humans.","volume":"22","author":"Johnson","year":"2012","journal-title":"Brain Pathol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/j.nbd.2011.12.005","article-title":"Targeting hyperphosphorylated tau with sodium selenate suppresses seizures in rodent models.","volume":"45","author":"Jones","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/960126","article-title":"Microtubule-associated proteins in mesial temporal lobe epilepsy with and without psychiatric comorbidities and their relation with granular cell layer dispersion.","volume":"2013","author":"Kandratavicius","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"B46","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/B978-0-12-802395-2.00025-0","article-title":"Tauopathies.","volume":"145","author":"Kovacs","year":"2017","journal-title":"Handb. Clin. Neurol."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2014.00047","article-title":"Blast TBI models, neuropathology, and implications for seizure risk.","volume":"5","author":"Kovacs","year":"2014","journal-title":"Front. Neurol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"e2259","DOI":"10.1212\/WNL.0000000000010612","article-title":"Association of epileptiform abnormalities and seizures in Alzheimer disease.","volume":"95","author":"Lam","year":"2020","journal-title":"Neurology"},{"key":"B49","doi-asserted-by":"publisher","first-page":"705","DOI":"10.3233\/JAD-2010-1276","article-title":"Lithium treatment arrests the development of neurofibrillary tangles in mutant tau transgenic mice with advanced neurofibrillary pathology.","volume":"19","author":"Leroy","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"B50","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.yebeh.2011.04.060","article-title":"Autism in Dravet syndrome: prevalence, features, and relationship to the clinical characteristics of epilepsy and mental retardation.","volume":"21","author":"Li","year":"2011","journal-title":"Epilepsy Behav."},{"key":"B51","doi-asserted-by":"publisher","first-page":"531","DOI":"10.3233\/JAD-2009-1069","article-title":"Dysregulation of tau phosphorylation in mouse brain during excitotoxic damage.","volume":"17","author":"Liang","year":"2009","journal-title":"J. Alzheimers Dis."},{"key":"B52","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1001\/jamaneurol.2019.4284","article-title":"Association of cognitive and behavioral features between adults with tuberous sclerosis and frontotemporal dementia.","volume":"77","author":"Liu","year":"2020","journal-title":"JAMA Neurol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.jocn.2016.10.012","article-title":"Dysregulation of PINCH signaling in mesial temporal epilepsy.","volume":"36","author":"Liu","year":"2017","journal-title":"J. Clin. Neurosci."},{"key":"B54","doi-asserted-by":"publisher","first-page":"e136","DOI":"10.1111\/epi.13847","article-title":"Accelerated kindling epileptogenesis in Tg4510 tau transgenic mice, but not in tau knockout mice.","volume":"58","author":"Liu","year":"2017","journal-title":"Epilepsia"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1093\/brain\/aww116","article-title":"Sodium selenate retards epileptogenesis in acquired epilepsy models reversing changes in protein phosphatase 2A and hyperphosphorylated tau.","volume":"139","author":"Liu","year":"2016","journal-title":"Brain"},{"key":"B56","first-page":"221","article-title":"N-methyl-D-aspartate receptors mediate epilepsy-induced axonal impairment and tau phosphorylation via activating glycogen synthase kinase-3beta and cyclin-dependent kinase 5.","volume":"23","author":"Liu","year":"2017","journal-title":"Discov. Med."},{"key":"B57","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.neuint.2013.01.014","article-title":"Rapamycin decreases tau phosphorylation at Ser214 through regulation of cAMP-dependent kinase.","volume":"62","author":"Liu","year":"2013","journal-title":"Neurochem. Int."},{"key":"B58","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1093\/brain\/118.1.119","article-title":"Neurofibrillary tangles in niemann-pick disease type C.","volume":"118","author":"Love","year":"1995","journal-title":"Brain"},{"key":"B59","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.expneurol.2012.04.008","article-title":"Ontogeny of Lafora bodies and neurocytoskeleton changes in Laforin-deficient mice.","volume":"236","author":"Machado-Salas","year":"2012","journal-title":"Exp. Neurol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.nbd.2014.05.033","article-title":"Bidirectional links between Alzheimer\u2019s disease and Niemann-Pick type C disease.","volume":"72","author":"Malnar","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"B61","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1111\/nan.12463","article-title":"Review: mechanistic target of rapamycin (mTOR) pathway, focal cortical dysplasia and epilepsy.","volume":"44","author":"Marsan","year":"2018","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"5546","DOI":"10.1523\/JNEUROSCI.5540-06.2007","article-title":"A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival.","volume":"27","author":"Meikle","year":"2007","journal-title":"J. Neurosci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.yebeh.2015.04.030","article-title":"Cerebrospinal fluid tau proteins in status epilepticus.","volume":"49","author":"Monti","year":"2015","journal-title":"Epilepsy Behav."},{"key":"B64","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/j.neuron.2011.04.009","article-title":"The many faces of tau.","volume":"70","author":"Morris","year":"2011","journal-title":"Neuron"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.01017","article-title":"Tau and mTOR: the hotspots for multifarious diseases in Alzheimer\u2019s development.","volume":"12","author":"Mueed","year":"2018","journal-title":"Front. Neurosci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1016\/j.neuron.2015.07.033","article-title":"Excitatory\/inhibitory balance and circuit homeostasis in autism spectrum disorders.","volume":"87","author":"Nelson","year":"2015","journal-title":"Neuron"},{"key":"B67","doi-asserted-by":"publisher","first-page":"6990","DOI":"10.1073\/pnas.0500466102","article-title":"Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo.","volume":"102","author":"Noble","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062459","article-title":"Rapamycin attenuates the progression of tau pathology in P301S tau transgenic mice.","volume":"8","author":"Ozcelik","year":"2013","journal-title":"PLoS One"},{"key":"B69","doi-asserted-by":"publisher","first-page":"548","DOI":"10.4161\/auto.5.4.8364","article-title":"Tau normal function influences Niemann-Pick type C disease pathogenesis in mice and modulates autophagy in NPC1-deficient cells.","volume":"5","author":"Pacheco","year":"2009","journal-title":"Autophagy"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.4103\/2152-7806.147566","article-title":"The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy.","volume":"5","author":"Petraglia","year":"2014","journal-title":"Surg. Neurol. Int."},{"key":"B71","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1007\/s00401-018-1909-9","article-title":"Nodding syndrome in Uganda is a tauopathy.","volume":"136","author":"Pollanen","year":"2018","journal-title":"Acta Neuropathol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/embor.2013.15","article-title":"Physiological release of endogenous tau is stimulated by neuronal activity.","volume":"14","author":"Pooler","year":"2013","journal-title":"EMBO Rep."},{"key":"B73","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1111\/bpa.12514","article-title":"Characterising subtypes of hippocampal sclerosis and reorganization: correlation with pre and postoperative memory deficit.","volume":"28","author":"Prada Jardim","year":"2018","journal-title":"Brain Pathol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"22657","DOI":"10.1074\/jbc.M109.009688","article-title":"Hyperphosphorylation and aggregation of Tau in laforin-deficient mice, an animal model for Lafora disease.","volume":"284","author":"Puri","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B75","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.brainres.2015.11.007","article-title":"Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy.","volume":"1630","author":"Puvenna","year":"2016","journal-title":"Brain Res."},{"key":"B76","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.yebeh.2014.11.014","article-title":"Features of autism spectrum disorder (ASD) in childhood epilepsy: a population-based study.","volume":"42","author":"Reilly","year":"2015","journal-title":"Epilepsy Behav."},{"key":"B77","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1126\/science.1141736","article-title":"Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer\u2019s disease mouse model.","volume":"316","author":"Roberson","year":"2007","journal-title":"Science"},{"key":"B78","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1089\/neu.2014.3548","article-title":"A novel, ultrasensitive assay for tau: potential for assessing traumatic brain injury in tissues and biofluids.","volume":"32","author":"Rubenstein","year":"2015","journal-title":"J. Neurotrauma"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19041092","article-title":"Tau-induced pathology in epilepsy and dementia: notions from patients and animal models.","volume":"19","author":"Sanchez","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"B80","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.braindev.2014.08.010","article-title":"Infantile tauopathies: hemimegalencephaly; tuberous sclerosis complex; focal cortical dysplasia 2; ganglioglioma.","volume":"37","author":"Sarnat","year":"2015","journal-title":"Brain Dev."},{"key":"B81","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1111\/j.1528-1167.2007.01107.x","article-title":"Pathological tau tangles localize to focal cortical dysplasia in older patients.","volume":"48","author":"Sen","year":"2007","journal-title":"Epilepsia"},{"key":"B82","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1159\/000109855","article-title":"The potential role of cyclin-dependent kinase 5 in focal cortical dysplasia.","volume":"30","author":"Sen","year":"2008","journal-title":"Dev. Neurosci."},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039152","article-title":"Mapping the spatio-temporal pattern of the mammalian target of rapamycin (mTOR) activation in temporal lobe epilepsy.","volume":"7","author":"Sha","year":"2012","journal-title":"PLoS One"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abm5527","article-title":"TAU ablation in excitatory neurons and postnatal TAU knockdown reduce epilepsy, SUDEP, and autism behaviors in a Dravet syndrome model.","volume":"14","author":"Shao","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1007\/s12098-021-03928-w","article-title":"Epilepsy and EEG abnormalities in children with autism spectrum disorders.","author":"Sharma","year":"2021","journal-title":"Indian J. Pediatr."},{"key":"B86","doi-asserted-by":"publisher","first-page":"3058","DOI":"10.1111\/epi.17086","article-title":"Low prevalence of amyloid and tau pathology in drug-resistant temporal lobe epilepsy.","volume":"62","author":"Silva","year":"2021","journal-title":"Epilepsia"},{"key":"B87","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/s0304-3940(02)00520-7","article-title":"Abnormal expression of cdk5 in focal cortical dysplasia in humans.","volume":"328","author":"Sisodiya","year":"2002","journal-title":"Neurosci. Lett."},{"key":"B88","doi-asserted-by":"publisher","first-page":"2398","DOI":"10.1111\/epi.16375","article-title":"Tau deposition in young adults with drug-resistant focal epilepsy.","volume":"60","author":"Smith","year":"2019","journal-title":"Epilepsia"},{"key":"B89","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1111\/epi.17115","article-title":"The epilepsy-autism spectrum disorder phenotype in the era of molecular genetics and precision therapy.","volume":"63","author":"Specchio","year":"2022","journal-title":"Epilepsia"},{"key":"B90","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1212\/WNL.0000000000002836","article-title":"Autism and epilepsy: a population-based nationwide cohort study.","volume":"87","author":"Sundelin","year":"2016","journal-title":"Neurology"},{"key":"B91","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/BF00309338","article-title":"Neurofibrillary tangles in Niemann-Pick disease type C.","volume":"89","author":"Suzuki","year":"1995","journal-title":"Acta Neuropathol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"421.e1","DOI":"10.1016\/j.neuron.2020.01.038","article-title":"Tau reduction prevents key features of autism in mouse models.","volume":"106","author":"Tai","year":"2020","journal-title":"Neuron"},{"key":"B93","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1111\/nan.12458","article-title":"Review: neurodegenerative processes in temporal lobe epilepsy with hippocampal sclerosis: clinical, pathological and neuroimaging evidence.","volume":"44","author":"Tai","year":"2018","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"2441","DOI":"10.1093\/brain\/aww187","article-title":"Hyperphosphorylated tau in patients with refractory epilepsy correlates with cognitive decline: a study of temporal lobe resections.","volume":"139","author":"Tai","year":"2016","journal-title":"Brain"},{"key":"B95","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1080\/02699052.2019.1667539","article-title":"The genetic ablation of tau improves long-term, but not short-term, functional outcomes after experimental traumatic brain injury in mice.","volume":"34","author":"Tan","year":"2020","journal-title":"Brain Inj"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/630853","article-title":"A review of the epidemiology of temporal lobe epilepsy.","volume":"2012","author":"Tellez-Zenteno","year":"2012","journal-title":"Epilepsy Res. Treat."},{"key":"B97","doi-asserted-by":"publisher","first-page":"2969","DOI":"10.1093\/brain\/awr209","article-title":"Neurofibrillary tangle pathology and Braak staging in chronic epilepsy in relation to traumatic brain injury and hippocampal sclerosis: a post-mortem study.","volume":"134","author":"Thom","year":"2011","journal-title":"Brain"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.00019","article-title":"GSK3beta and Tau protein in Alzheimer\u2019s disease and epilepsy.","volume":"14","author":"Toral-Rios","year":"2020","journal-title":"Front. Cell Neurosci."},{"key":"B99","doi-asserted-by":"publisher","first-page":"4094","DOI":"10.1093\/hmg\/dds238","article-title":"MAPT expression and splicing is differentially regulated by brain region: relation to genotype and implication for tauopathies.","volume":"21","author":"Trabzuni","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"B100","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1080\/14737175.2017.1244482","article-title":"Targeting mTOR to reduce Alzheimer-related cognitive decline: from current hits to future therapies.","volume":"17","author":"Tramutola","year":"2017","journal-title":"Expert Rev. Neurother."},{"key":"B101","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.eplepsyres.2015.04.004","article-title":"Effect of epileptic seizures on the cerebrospinal fluid\u2013A systematic retrospective analysis.","volume":"114","author":"Tumani","year":"2015","journal-title":"Epilepsy Res."},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067797","article-title":"Clinical characteristics of children with autism spectrum disorder and co-occurring epilepsy.","volume":"8","author":"Viscidi","year":"2013","journal-title":"PLoS One"},{"key":"B103","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1002\/ana.24794","article-title":"Incidence and impact of subclinical epileptiform activity in Alzheimer\u2019s disease.","volume":"80","author":"Vossel","year":"2016","journal-title":"Ann. Neurol."},{"key":"B104","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/S1474-4422(17)30044-3","article-title":"Epileptic activity in Alzheimer\u2019s disease: causes and clinical relevance.","volume":"16","author":"Vossel","year":"2017","journal-title":"Lancet Neurol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/nrn.2015.1","article-title":"Tau in physiology and pathology.","volume":"17","author":"Wang","year":"2016","journal-title":"Nat. Rev. Neurosci."},{"key":"B106","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.neurobiolaging.2014.07.035","article-title":"Cross talk between PI3K-AKT-GSK-3beta and PP2A pathways determines tau hyperphosphorylation.","volume":"36","author":"Wang","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"B107","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/j.1528-1167.2009.02341.x","article-title":"Mammalian target of rapamycin (mTOR) inhibition as a potential antiepileptogenic therapy: from tuberous sclerosis to common acquired epilepsies.","volume":"51","author":"Wong","year":"2010","journal-title":"Epilepsia"},{"key":"B108","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1111\/j.1469-8749.2012.04223.x","article-title":"A systematic review of two outcomes in autism spectrum disorder - epilepsy and mortality.","volume":"54","author":"Woolfenden","year":"2012","journal-title":"Dev. Med. Child Neurol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/j.mehy.2011.03.003","article-title":"Is intractable epilepsy a tauopathy?","volume":"76","author":"Xi","year":"2011","journal-title":"Med. Hypotheses."},{"key":"B110","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1002\/syn.20681","article-title":"Gene expression analysis on anterior temporal neocortex of patients with intractable epilepsy.","volume":"63","author":"Xi","year":"2009","journal-title":"Synapse"},{"key":"B111","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1084\/jem.20131685","article-title":"Neuronal activity regulates extracellular tau in vivo.","volume":"211","author":"Yamada","year":"2014","journal-title":"J. Exp. Med."},{"key":"B112","doi-asserted-by":"publisher","first-page":"2685","DOI":"10.1093\/brain\/awy193","article-title":"Induction of a transmissible tau pathology by traumatic brain injury.","volume":"141","author":"Zanier","year":"2018","journal-title":"Brain"},{"key":"B113","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1002\/ana.21331","article-title":"Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex.","volume":"63","author":"Zeng","year":"2008","journal-title":"Ann. Neurol."},{"key":"B114","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1111\/j.1471-4159.2008.05657.x","article-title":"Mitogen-activated protein kinase activity may not be necessary for the neuropathology of Niemann-Pick type C mice.","volume":"107","author":"Zhang","year":"2008","journal-title":"J. Neurochem."},{"key":"B115","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1016\/S0002-9440(10)63347-0","article-title":"Cyclin-dependent kinase inhibitors attenuate protein hyperphosphorylation, cytoskeletal lesion formation, and motor defects in Niemann-Pick Type C mice.","volume":"165","author":"Zhang","year":"2004","journal-title":"Am. J. Pathol."},{"key":"B116","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1007\/s12035-013-8601-9","article-title":"Hyperphosphorylated tau is implicated in acquired epilepsy and neuropsychiatric comorbidities.","volume":"49","author":"Zheng","year":"2014","journal-title":"Mol. Neurobiol."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.903973\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T06:47:42Z","timestamp":1658126862000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.903973\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,18]]},"references-count":116,"alternative-id":["10.3389\/fnagi.2022.903973"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2022.903973","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,18]]},"article-number":"903973"}}