{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:53:42Z","timestamp":1790045622335,"version":"4.0.1"},"reference-count":70,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T00:00:00Z","timestamp":1673913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["AACSFD\u201022\u2010974008"],"award-info":[{"award-number":["AACSFD\u201022\u2010974008"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Alzheimer's disease (AD) patients have a high risk of developing mesial temporal lobe epilepsy (MTLE) and subclinical epileptiform activity. MTLE in AD worsens outcomes. Therefore, we need to understand the overlap between these disease processes. We hypothesize that AD with MTLE represents a distinct subtype of AD, with the interplay between tau and epileptiform activity at its core. We discuss shared pathological features including histopathology, an initial mesial temporal lobe (MTL) hyperexcitability followed by MTL dysfunction and involvement of same networks in memory (AD) and seizures (MTLE). We provide evidence that tau accumulation linearly increases neuronal hyperexcitability, neuronal hyper\u2010excitability increases tau secretion, tau can provoke seizures, and tau reduction protects against seizures. We speculate that AD genetic mutations increase tau, which causes proportionate neuronal loss and\/or hyperexcitability, leading to seizures. We discuss that tau burden in MTLE predicts cognitive deficits among (1) AD and (2) MTLE without AD. Finally, we explore the possibility that anti\u2010seizure medications improve cognition by reducing neuronal hyper\u2010excitability, which reduces seizures and tau accumulation and spread.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>We hypothesize that patients with Alzheimer's disease (AD) and mesial temporal lobe epilepsy (MTLE) represents a distinct subtype of AD.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>AD and MTLE share histopathological features and involve overlapping neuronal and cortical networks.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Hyper\u2010phosphorylated tau (pTau) increases neuronal excitability and provoke seizures, neuronal excitability increases pTau, and pTau reduction reduces neuronal excitability and protects against seizures.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The pTau burden in MTL predicts cognitive deficits among (1) AD and (2) MTLE without AD.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We speculate that anti\u2010seizure medications improve cognition by reducing neuronal excitability, which reduces seizures and pTau.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.12943","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T08:34:11Z","timestamp":1673944451000},"page":"2697-2706","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Does Alzheimer's disease with mesial temporal lobe epilepsy represent a distinct disease subtype?"],"prefix":"10.1002","volume":"19","author":[{"given":"Ifrah","family":"Zawar","sequence":"first","affiliation":[{"name":"Department of Neurology University of Virginia School of Medicine  Charlottesville Virginia US"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaideep","family":"Kapur","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia School of Medicine  Charlottesville Virginia US"},{"name":"Department of Neuroscience University of Virginia  Charlottesville Virginia US"},{"name":"Department of UVA brain institute University of Virginia  Charlottesville Virginia US"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0963\u20107214.2004.00293.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/MSJ.20157"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(19)33064\u20108"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen\u20102019\u2010035767"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000011080"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2009.130"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/EPI.12045"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/20.Supplement_2.S36"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.ARR.2021.101478"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13744"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2021.108006"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755\u20105949.2011.00251.x"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000117218"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/OXFORDJOURNALS.AJE.A117597"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.06.015"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ANA.24794"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010612"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4330"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(17)30044\u20103"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.neuropsych.15060143"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.00021"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010neuro\u2010080317\u2010061725"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/FNEUR.2019.00601"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/SCIENCE.AAU8956"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/NM.4084"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.42.3.631"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JALZ.2011.03.005"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.16\u201014\u201004491.1996"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201015701\u20102"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww187"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/BRAIN\/AWR209"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy022"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4152\u201010.2011"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010011\u20100879\u2010y"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318232a379"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2013.968"},{"key":"e_1_2_6_39_1","article-title":"Antiepileptic effect of electric stimulation of the locus coeruleus in man","author":"Faber J","year":"1983","journal-title":"Act Nerv Super (Praha)"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1159\/000099484"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4740\u201011.2011"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1146\/ANNUREV\u2010NEURO\u2010080317\u2010061725"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017\u2010009\u20108109\u20107"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201541439"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.06.036"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3191\u201012.2013"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4328"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2107\u201013.2013"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12349"},{"key":"e_1_2_6_50_1","article-title":"Amyloid\u2010\u03b2 induced neuronal dysfunction in Alzheimer's disease\u202f: from synapses toward neural networks","author":"Palop JJ","year":"2011","journal-title":"Nat Neurosci"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5215\u201008.2009"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2012.05.048"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4040\u201010.2010"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24016"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2015.08.004"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2011.03.022"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000063311.58879.01"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010019\u201002036\u20106"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww027"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau5732"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1992.00530340054018"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/BRAIN\/AWAB268"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1159\/000106956"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/BRAIN\/AWAA284"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.1708"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0511065103"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00633204"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1073\/PNAS.1121081109"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELREP.2017.06.040"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2021.3310"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2552\u201014.2015"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.12943","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.12943","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.12943","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:54:42Z","timestamp":1759971282000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.12943"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,17]]},"references-count":70,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/alz.12943"],"URL":"https:\/\/doi.org\/10.1002\/alz.12943","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,17]]},"assertion":[{"value":"2022-09-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}