{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:13:13Z","timestamp":1785413593186,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,13]]},"group-title":"Neuroscience","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["NS102730"],"award-info":[{"award-number":["NS102730"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001642","name":"Glenn Foundation for Medical Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001642","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,13]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Aberrant neuronal activity is an early pathological feature of numerous neurodegenerative disorders, including tauopathy, and is thought to play a role in disease progression. However, the mechanism underlying abnormal neuronal activity remains elusive. Here, we reveal a relationship between DNA double-strand break (DSB)\/p53 pathway activation and aberrant neuronal activity. Activating p53 as part of the DNA damage response via DSB induction, or by preventing MDM2-mediated p53 degradation, causes aberrant activity in both mouse and human neurons. p53 activation induces the expression of genes regulating synaptic transmission, and p53-responsive gene upregulation is overrepresented in\n                  <jats:italic>postmortem<\/jats:italic>\n                  human Alzheimer\u2019s disease neurons burdened with neurofibrillary tangles (NFTs). Using a human iPSC-based cerebral organoid model of frontotemporal dementia that exhibits relevant pathologies including elevated DSBs, aberrant neuronal activity, and NFTs, we show that inhibiting p53 transcriptional activity with a small molecule ameliorates aberrant calcium fluctuations in neurons. Together, our findings highlight p53 inhibition as a novel therapeutic strategy to counter aberrant neuronal activity in neurodegenerative diseases characterized by tauopathy.\n                <\/jats:p>","DOI":"10.64898\/2026.05.11.724110","type":"posted-content","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T21:35:13Z","timestamp":1778708113000},"source":"Crossref","is-referenced-by-count":0,"title":["DNA double-strand break signaling induces aberrant neuronal activity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6788-7185","authenticated-orcid":false,"given":"Ping-Chieh","family":"Pao","sequence":"first","affiliation":[{"name":"Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Neurology Research Therapeutic Area, Sanofi, Cambridge, MA 02141"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwang","family":"Liu","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Ashley","family":"Watson","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Developmental and Cognitive Genomics Research Laboratory, Division of Biological Sciences, Section of Neurobiology, University of California, San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Lee","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Seguin","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiyun","family":"Dong","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samaa","family":"Rasheed","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Division of Newborn Medicine, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Staab","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ois\u00edn","family":"King","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Geigenm\u00fcller","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Penney","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Department of Biomedical Sciences, AVC, University of Prince Edward Island, Charlottetown, PE, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Gao","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdurrahman","family":"Muhtaseb","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravikiran M.","family":"Raju","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Division of Newborn Medicine, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1262-0592","authenticated-orcid":false,"given":"Li-Huei","family":"Tsai","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026051516551147000_2026.05.11.724110v1.1","doi-asserted-by":"crossref","unstructured":"Adamec E , Vonsattel JP & Nixon RA (1999) DNA strand breaks in Alzheimer\u2019s disease. Brain Res","DOI":"10.1097\/00005072-199905000-00092"},{"key":"2026051516551147000_2026.05.11.724110v1.2","doi-asserted-by":"crossref","unstructured":"Allen BD , Syage AR , Maroso M , Baddour AAD , Luong V , Minasyan H , Giedzinski E , West BL , Soltesz I , Limoli CL , et al (2020) Mitigation of helium irradiation-induced brain injury by microglia depletion. J Neuroinflammation","DOI":"10.1186\/s12974-020-01790-9"},{"key":"2026051516551147000_2026.05.11.724110v1.3","doi-asserted-by":"crossref","unstructured":"Asada-Utsugi M , Uemura K , Ayaki T , T. Uemura M , Minamiyama S , Hikiami R , Morimura T , Shodai A , Ueki T , Takahashi R , et al (2022) Failure of DNA double-strand break repair by tau mediates Alzheimer\u2019s disease pathology in vitro. Commun Biol 5","DOI":"10.1038\/s42003-022-03312-0"},{"key":"2026051516551147000_2026.05.11.724110v1.4","doi-asserted-by":"crossref","unstructured":"Beagle AJ , Darwish SM , Ranasinghe KG , La AL , Karageorgiou E & Vossel KA (2017) Relative incidence of seizures and myoclonus in Alzheimer\u2019s disease, dementia with lewy bodies, and frontotemporal dementia. J Alzheimer\u2019s Dis","DOI":"10.3233\/JAD-170031"},{"key":"2026051516551147000_2026.05.11.724110v1.5","doi-asserted-by":"crossref","unstructured":"Bero AW , Yan P , Roh JH , Cirrito JR , Stewart FR , Raichle ME , Lee JM & Holtzman DM (2011) Neuronal activity regulates the regional vulnerability to amyloid-\u03b2 2 deposition. Nat Neurosci","DOI":"10.1038\/nn.2801"},{"key":"2026051516551147000_2026.05.11.724110v1.6","doi-asserted-by":"crossref","unstructured":"Crimins JL , Rocher AB , Peters A , Shultz P , Lewis J & Luebke JI (2011) Homeostatic responses by surviving cortical pyramidal cells in neurodegenerative tauopathy. Acta Neuropathol","DOI":"10.1007\/s00401-011-0877-0"},{"key":"2026051516551147000_2026.05.11.724110v1.7","doi-asserted-by":"crossref","unstructured":"Dileep V , Boix CA , Mathys H , Marco A , Welch GM , Meharena HS , Loon A , Jeloka R , Peng Z , Bennett DA , et al (2023) Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration. Cell 186","DOI":"10.1016\/j.cell.2023.08.038"},{"key":"2026051516551147000_2026.05.11.724110v1.8","doi-asserted-by":"crossref","unstructured":"Dobbin MM , Madabhushi R , Pan L , Chen Y , Kim D , Gao J , Ahanonu B , Pao PC , Qiu Y , Zhao Y , et al (2013) SIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons. Nat Neurosci","DOI":"10.1038\/nn.3460"},{"key":"2026051516551147000_2026.05.11.724110v1.9","doi-asserted-by":"crossref","unstructured":"Gazestani V , Kamath T , Nadaf NM , Dougalis A , Burris SJ , Rooney B , Junkkari A , Vanderburg C , Pelkonen A , Gomez-Budia M , et al (2023) Early Alzheimer\u2019s disease pathology in human cortex involves transient cell states. Cell 186","DOI":"10.1016\/j.cell.2023.08.005"},{"key":"2026051516551147000_2026.05.11.724110v1.10","doi-asserted-by":"crossref","unstructured":"Jenrow KA , Ratkewicz AE & Elisevich K V. (2001) Enhanced excitability induced by ionizing radiation in the kindled rat. Exp Neurol","DOI":"10.1006\/exnr.2000.7616"},{"key":"2026051516551147000_2026.05.11.724110v1.11","doi-asserted-by":"crossref","unstructured":"Komulainen E , Badman J , Rey S , Rulten S , Ju L , Fennell K , Kalasova I , Ilievova K , McKinnon PJ , Hanzlikova H , et al (2021) Parp1 hyperactivity couples DNA breaks to aberrant neuronal calcium signalling and lethal seizures. EMBO Rep","DOI":"10.15252\/embr.202051851"},{"key":"2026051516551147000_2026.05.11.724110v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401925"},{"key":"2026051516551147000_2026.05.11.724110v1.13","doi-asserted-by":"crossref","unstructured":"Love MI , Huber W & Anders S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2026051516551147000_2026.05.11.724110v1.14","doi-asserted-by":"crossref","unstructured":"Madabhushi R , Gao F , Pfenning AR , Pan L , Yamakawa S , Seo J , Rueda R , Phan TX , Yamakawa H , Pao PC , et al (2015) Activity-Induced DNA Breaks Govern the Expression of Neuronal Early-Response Genes. Cell","DOI":"10.1016\/j.cell.2015.05.032"},{"key":"2026051516551147000_2026.05.11.724110v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.06.034"},{"key":"2026051516551147000_2026.05.11.724110v1.16","doi-asserted-by":"crossref","unstructured":"Marty VN , Vlkolinsky R , Minassian N , Cohen T , Nelson GA & Spigelman I (2014) Radiation-induced alterations in synaptic neurotransmission of dentate granule cells depend on the dose and species of charged particles. Radiat Res","DOI":"10.1667\/RR13647.1"},{"key":"2026051516551147000_2026.05.11.724110v1.17","doi-asserted-by":"crossref","unstructured":"Mathys H , Peng Z , Boix CA , Victor MB , Leary N , Babu S , Abdelhady G , Jiang X , Ng AP , Ghafari K , et al (2023) Single-cell atlas reveals correlates of high cognitive function, dementia, and resilience to Alzheimer\u2019s disease pathology. Cell 186","DOI":"10.1016\/j.cell.2023.08.039"},{"key":"2026051516551147000_2026.05.11.724110v1.18","doi-asserted-by":"crossref","unstructured":"Merino-Serrais P , Benavides-Piccione R , Blazquez-Llorca L , Kastanauskaite A , R\u00e1bano A , Avila J & Defelipe J (2013) The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer\u2019s disease. Brain","DOI":"10.1093\/brain\/awt088"},{"key":"2026051516551147000_2026.05.11.724110v1.19","doi-asserted-by":"crossref","unstructured":"Merlo P , Frost B , Peng S , Yang YJ , Park PJ & Feany M (2014) P53 prevents neurodegeneration by regulating synaptic genes. Proc Natl Acad Sci U S A","DOI":"10.1073\/pnas.1419083111"},{"key":"2026051516551147000_2026.05.11.724110v1.20","doi-asserted-by":"crossref","unstructured":"Mucke L & Selkoe DJ (2012) Neurotoxicity of amyloid \u03b2-protein: Synaptic and network dysfunction. Cold Spring Harb Perspect Med 2","DOI":"10.1101\/cshperspect.a006338"},{"key":"2026051516551147000_2026.05.11.724110v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01222-2"},{"key":"2026051516551147000_2026.05.11.724110v1.22","doi-asserted-by":"crossref","unstructured":"Otero-Garcia M , Mahajani SU , Wakhloo D , Tang W , Xue YQ , Morabito S , Pan J , Oberhauser J , Madira AE , Shakouri T , et al (2022) Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer\u2019s disease. Neuron 110","DOI":"10.1016\/j.neuron.2022.06.021"},{"key":"2026051516551147000_2026.05.11.724110v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2016.141"},{"key":"2026051516551147000_2026.05.11.724110v1.24","doi-asserted-by":"crossref","unstructured":"Pao PC , Penney J & Tsai LH (2019) Examining the role of HDACs in DNA double-strand break repair in neurons. In Methods in Molecular Biology","DOI":"10.1007\/978-1-4939-9434-2_13"},{"key":"2026051516551147000_2026.05.11.724110v1.25","doi-asserted-by":"crossref","unstructured":"Qian X , Nguyen HN , Song MM , Hadiono C , Ogden SC , Hammack C , Yao B , Hamersky GR , Jacob F , Zhong C , et al (2016) Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure. Cell","DOI":"10.1016\/j.cell.2016.04.032"},{"key":"2026051516551147000_2026.05.11.724110v1.26","doi-asserted-by":"crossref","unstructured":"Raja WK , Mungenast AE , Lin YT , Ko T , Abdurrob F , Seo J & Tsai LH (2016) Self-organizing 3D human neural tissue derived from induced pluripotent stem cells recapitulate Alzheimer\u2019s disease phenotypes. PLoS One","DOI":"10.1371\/journal.pone.0161969"},{"key":"2026051516551147000_2026.05.11.724110v1.27","doi-asserted-by":"crossref","unstructured":"Risso D , Ngai J , Speed TP & Dudoit S (2014) Normalization of RNA-seq data using factor analysis of control genes or samples. Nat Biotechnol 32","DOI":"10.1038\/nbt.2931"},{"key":"2026051516551147000_2026.05.11.724110v1.28","doi-asserted-by":"crossref","unstructured":"Rudobeck E , Bellone JA , Sz\u00fccs A , Bonnick K , Mehrotra-Carter S , Badaut J , Nelson GA , Hartman RE & Vlkolinsk\u00fd R (2017) Low-dose proton radiation effects in a transgenic mouse model of Alzheimer\u2019s disease \u2013 Implications for space travel. PLoS One","DOI":"10.1371\/journal.pone.0186168"},{"key":"2026051516551147000_2026.05.11.724110v1.29","doi-asserted-by":"crossref","unstructured":"Samarasinghe RA , Miranda OA , Buth JE , Mitchell S , Ferando I , Watanabe M , Allison TF , Kurdian A , Fotion NN , Gandal MJ , et al (2021) Identification of neural oscillations and epileptiform changes in human brain organoids. Nat Neurosci","DOI":"10.1038\/s41593-021-00906-5"},{"key":"2026051516551147000_2026.05.11.724110v1.30","doi-asserted-by":"crossref","unstructured":"Sanchez PE , Zhu L , Verret L , Vossel KA , Orr AG , Cirrito JR , Devidze N , Ho K , Yu GQ , Palop JJ , et al (2012) Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer\u2019s disease model. Proc Natl Acad Sci U S A","DOI":"10.1073\/pnas.1121081109"},{"key":"2026051516551147000_2026.05.11.724110v1.31","doi-asserted-by":"crossref","unstructured":"Seo J , Kritskiy O , Ashley Watson L , Barker SJ , Dey D , Raja WK , Lin YT , Ko T , Cho S , Penney J , et al (2017) Inhibition of p25\/Cdk5 attenuates tauopathy in mouse and iPSC models of frontotemporal dementia. J Neurosci","DOI":"10.1523\/JNEUROSCI.0621-17.2017"},{"key":"2026051516551147000_2026.05.11.724110v1.32","doi-asserted-by":"crossref","unstructured":"Shanbhag NM , Evans MD , Mao W , Nana AL , Seeley WW , Adame A , Rissman RA , Masliah E & Mucke L (2019) Early neuronal accumulation of DNA double strand breaks in Alzheimer\u2019s disease. Acta Neuropathol Commun","DOI":"10.1186\/s40478-019-0723-5"},{"key":"2026051516551147000_2026.05.11.724110v1.33","doi-asserted-by":"crossref","unstructured":"Simpson JE , Ince PG , Matthews FE , Shaw PJ , Heath PR , Brayne C , Garwood C , Higginbottom A & Wharton SB (2015) A neuronal DNA damage response is detected at the earliest stages of Alzheimer\u2019s neuropathology and correlates with cognitive impairment in the Medical Research Council\u2019s Cognitive Function and Ageing Study ageing brain cohort. Neuropathol Appl Neurobiol","DOI":"10.1111\/nan.12202"},{"key":"2026051516551147000_2026.05.11.724110v1.34","doi-asserted-by":"crossref","unstructured":"Srivastava M , Nambiar M , Sharma S , Karki SS , Goldsmith G , Hegde M , Kumar S , Pandey M , Singh RK , Ray P , et al (2012) An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression. Cell 151","DOI":"10.1016\/j.cell.2012.11.054"},{"key":"2026051516551147000_2026.05.11.724110v1.35","doi-asserted-by":"crossref","unstructured":"Suberbielle E , Djukic B , Evans M , Kim DH , Taneja P , Wang X , Finucane M , Knox J , Ho K , Devidze N , et al (2015) DNA repair factor BRCA1 depletion occurs in Alzheimer brains and impairs cognitive function in mice. Nat Commun","DOI":"10.1038\/ncomms9897"},{"key":"2026051516551147000_2026.05.11.724110v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-02024-7"},{"key":"2026051516551147000_2026.05.11.724110v1.37","doi-asserted-by":"crossref","unstructured":"Thadathil N , Delotterie DF , Xiao J , Hori R , McDonald MP & Khan MM (2021) DNA Double-Strand Break Accumulation in Alzheimer\u2019s Disease: Evidence from Experimental Models and Postmortem Human Brains. Mol Neurobiol 58","DOI":"10.1007\/s12035-020-02109-8"},{"key":"2026051516551147000_2026.05.11.724110v1.38","doi-asserted-by":"crossref","unstructured":"Vassilev LT , Vu BT , Graves B , Carvajal D , Podlaski F , Filipovic Z , Kong N , Kammlott U , Lukacs C , Klein C , et al (2004) In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2. Science (80-) 303","DOI":"10.1126\/science.1092472"},{"key":"2026051516551147000_2026.05.11.724110v1.39","doi-asserted-by":"crossref","unstructured":"Venkatesh HS , Johung TB , Caretti V , Noll A , Tang Y , Nagaraja S , Gibson EM , Mount CW , Polepalli J , Mitra SS , et al (2015) Neuronal activity promotes glioma growth through neuroligin-3 secretion. Cell","DOI":"10.1016\/j.cell.2015.04.012"},{"key":"2026051516551147000_2026.05.11.724110v1.40","doi-asserted-by":"crossref","unstructured":"Vossel K , Ranasinghe KG , Beagle AJ , La A , Ah Pook K , Castro M , Mizuiri D , Honma SM , Venkateswaran N , Koestler M , et al (2021) Effect of Levetiracetam on Cognition in Patients with Alzheimer Disease with and without Epileptiform Activity: A Randomized Clinical Trial. JAMA Neurol","DOI":"10.1001\/jamaneurol.2021.3310"},{"key":"2026051516551147000_2026.05.11.724110v1.41","doi-asserted-by":"crossref","unstructured":"Vossel KA , Ranasinghe KG , Beagle AJ , Mizuiri D , Honma SM , Dowling AF , Darwish SM , Van Berlo V , Barnes DE , Mantle M , et al (2016) Incidence and impact of subclinical epileptiform activity in Alzheimer\u2019s disease. Ann Neurol","DOI":"10.1002\/ana.24794"},{"key":"2026051516551147000_2026.05.11.724110v1.42","doi-asserted-by":"crossref","unstructured":"Wang WY , Pan L , Su SC , Quinn EJ , Sasaki M , Jimenez JC , MacKenzie IRA , Huang EJ & Tsai LH (2013) Interaction of FUS and HDAC1 regulates DNA damage response and repair in neurons. Nat Neurosci","DOI":"10.1038\/nn.3514"},{"key":"2026051516551147000_2026.05.11.724110v1.43","doi-asserted-by":"crossref","unstructured":"Wu JW , Hussaini SA , Bastille IM , Rodriguez GA , Mrejeru A , Rilett K , Sanders DW , Cook C , Fu H , Boonen RACM , et al (2016) Neuronal activity enhances tau propagation and tau pathology in vivo. Nat Neurosci","DOI":"10.1038\/nn.4328"},{"key":"2026051516551147000_2026.05.11.724110v1.44","doi-asserted-by":"crossref","unstructured":"Wu Q , Shaikh MA , Meymand ES , Zhang B , Luk KC , Trojanowski JQ & Lee VMY (2020) Neuronal activity modulates alpha-synuclein aggregation and spreading in organotypic brain slice cultures and in vivo. Acta Neuropathol","DOI":"10.1007\/s00401-020-02227-6"},{"key":"2026051516551147000_2026.05.11.724110v1.45","doi-asserted-by":"crossref","unstructured":"Yuan P & Grutzendler J (2016) Attenuation of \u03b2-amyloid deposition and neurotoxicity by chemogenetic modulation of neural activity. J Neurosci","DOI":"10.1523\/JNEUROSCI.2531-15.2016"},{"key":"2026051516551147000_2026.05.11.724110v1.46","doi-asserted-by":"crossref","unstructured":"Zhu Q , Niu Y , Gundry M & Zong C (2021) Single-cell damagenome profiling unveils vulnerable genes and functional pathways in human genome toward DNA damage. Sci Adv 7","DOI":"10.1126\/sciadv.abf3329"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.05.11.724110","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T23:55:22Z","timestamp":1778889322000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.05.11.724110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":46,"URL":"https:\/\/doi.org\/10.64898\/2026.05.11.724110","relation":{},"subject":[],"published":{"date-parts":[[2026,5,13]]},"subtype":"preprint"}}