{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T19:25:38Z","timestamp":1780514738906,"version":"3.54.1"},"reference-count":101,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["RF1 AG059088, R21 AG065914"],"award-info":[{"award-number":["RF1 AG059088, R21 AG065914"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS102227, and RF1 NS123457"],"award-info":[{"award-number":["R01 NS102227, and RF1 NS123457"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Psychiatry"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Age, female sex, and apolipoprotein E4 (E4) are risk factors to develop Alzheimer\u2019s disease (AD). There are three major human apoE isoforms: E2, E3, and E4. Compared to E3, E4 increases while E2 decreases AD risk. However, E2 is associated with increased risk and severity of post-traumatic stress disorder (PTSD). In cognitively healthy adults, E4 carriers have greater brain activation during learning and memory tasks in the absence of behavioral differences. Human apoE targeted replacement (TR) mice display differences in fear extinction that parallel human data: E2 mice show impaired extinction, mirroring heightened PTSD symptoms in E2 combat veterans. Recently, an adaptive role of DNA double strand breaks (DSBs) in immediate early gene expression (IEG) has been described. Age and disease synergistically increase DNA damage and decrease DNA repair. As the mechanisms underlying the relative risks of apoE, sex, and their interactions in aging are unclear, we used young (3 months) and middle-aged (12 months) male and female TR mice to investigate the influence of these factors on DSBs and IEGs at baseline and following contextual fear conditioning. We assessed brain-wide changes in neural activation following fear conditioning using whole-brain cFos imaging in young female TR mice. E4 mice froze more during fear conditioning and had lower cFos immunoreactivity across regions important for somatosensation and contextual encoding compared to E2 mice. E4 mice also showed altered co-activation compared to E3 mice, corresponding to human MRI and cognitive data, and indicating that there are differences in brain activity and connectivity at young ages independent of fear learning. There were increased DSB markers in middle-aged animals and alterations to cFos levels dependent on sex and isoform, as well. The increase in hippocampal DSB markers in middle-aged animals and female E4 mice may play a role in the risk for developing AD.<\/jats:p>","DOI":"10.1038\/s41380-023-01966-8","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T11:06:30Z","timestamp":1675335990000},"page":"3343-3354","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Age, sex, and apolipoprotein E isoform alter contextual fear learning, neuronal activation, and baseline DNA damage in the hippocampus"],"prefix":"10.1038","volume":"28","author":[{"given":"Sydney Weber","family":"Boutros","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Zimmerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney C.","family":"Nagy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek K.","family":"Unni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9861-9893","authenticated-orcid":false,"given":"Jacob","family":"Raber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"1966_CR1","doi-asserted-by":"publisher","first-page":"167","DOI":"10.2741\/E605","volume":"5","author":"I Piaceri","year":"2013","unstructured":"Piaceri I, Nacmias B, Sorbi S. Genetics of familial and sporadic Alzheimer\u2019s disease. Front Biosci (Elite Ed). 2013;5:167\u201377.","journal-title":"Front Biosci (Elite Ed)"},{"key":"1966_CR2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-015-0232-5","volume":"7","author":"R Guerreiro","year":"2015","unstructured":"Guerreiro R, Bras J. The age factor in Alzheimer\u2019s disease. Genome Med. 2015;7:106.","journal-title":"Genome Med"},{"key":"1966_CR3","first-page":"225","volume":"5","author":"O Scheyer","year":"2018","unstructured":"Scheyer O, Rahman A, Hristov H, Berkowitz C, Isaacson RS, Diaz Brinton R, et al. Female sex and Alzheimer\u2019s Risk: The menopause connection. J Prev Alzheimers Dis. 2018;5:225\u201330.","journal-title":"J Prev Alzheimers Dis"},{"key":"1966_CR4","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.jalz.2007.04.381","volume":"3","author":"R Brookmeyer","year":"2007","unstructured":"Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer\u2019s disease. Alzheimers Dement. 2007;3:186\u201391.","journal-title":"Alzheimers Dement"},{"key":"1966_CR5","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.neurobiolaging.2003.12.023","volume":"25","author":"J Raber","year":"2004","unstructured":"Raber J, Huang Y, Ashford JW. ApoE genotype accounts for the vast majority of AD risk and AD pathology. Neurobiol Aging. 2004;25:641\u201350.","journal-title":"Neurobiol Aging"},{"key":"1966_CR6","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1001\/jama.1997.03550160069041","volume":"278","author":"LA Farrer","year":"1997","unstructured":"Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997;278:1349\u201356.","journal-title":"JAMA"},{"key":"1966_CR7","doi-asserted-by":"crossref","unstructured":"Suchy-Dicey A, Howard B, Longstreth WT, Jr., Reiman EM, Buchwald D. APOE genotype, hippocampus, and cognitive markers of Alzheimer\u2019s disease in American Indians: Data from the Strong Heart Study. Alzheimers Dement. 2022;18:2518\u201326.","DOI":"10.1002\/alz.12573"},{"key":"1966_CR8","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1186\/s13195-021-00855-y","volume":"13","author":"MA Beydoun","year":"2021","unstructured":"Beydoun MA, Weiss J, Beydoun HA, Hossain S, Maldonado AI, Shen B, et al. Race, APOE genotypes, and cognitive decline among middle-aged urban adults. Alzheimers Res Ther. 2021;13:120.","journal-title":"Alzheimers Res Ther"},{"key":"1966_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-01848-7","volume":"12","author":"ERS Torres","year":"2022","unstructured":"Torres ERS, Luo J, Boehnlein JK, Towns D, Kinzie JD, DeBarber AE, et al. Apolipoprotein E Isoform-specific changes related to stress and trauma exposure. Transl Psychiatry. 2022;12:125.","journal-title":"Transl Psychiatry"},{"key":"1966_CR10","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1002\/da.22138","volume":"30","author":"TY Kim","year":"2013","unstructured":"Kim TY, Chung HG, Shin HS, Kim SJ, Choi JH, Chung MY, et al. Apolipoprotein E gene polymorphism, alcohol use, and their interactions in combat-related posttraumatic stress disorder. Depress Anxiety. 2013;30:1194\u2013201.","journal-title":"Depress Anxiety"},{"key":"1966_CR11","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.1038\/npp.2015.95","volume":"40","author":"LA Johnson","year":"2015","unstructured":"Johnson LA, Zuloaga DG, Bidiman E, Marzulla T, Weber S, Wahbeh H, et al. ApoE2 Exaggerates PTSD-Related Behavioral, Cognitive, and Neuroendocrine Alterations. Neuropsychopharmacology. 2015;40:2443\u201353.","journal-title":"Neuropsychopharmacology"},{"key":"1966_CR12","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1038\/s41591-020-0879-3","volume":"26","author":"BN Ostendorf","year":"2020","unstructured":"Ostendorf BN, Bilanovic J, Adaku N, Tafreshian KN, Tavora B, Vaughan RD, et al. Common germline variants of the human APOE gene modulate melanoma progression and survival. Nat Med. 2020;26:1048\u201353.","journal-title":"Nat Med"},{"key":"1966_CR13","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1203\/PDR.0b013e3181cb8e68","volume":"67","author":"SF Acevedo","year":"2010","unstructured":"Acevedo SF, Piper BJ, Craytor MJ, Benice TS, Raber J. Apolipoprotein E4 and sex affect neurobehavioral performance in primary school children. Pediatr Res. 2010;67:293\u20139.","journal-title":"Pediatr Res"},{"key":"1966_CR14","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1073\/pnas.2635903100","volume":"101","author":"EM Reiman","year":"2004","unstructured":"Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, et al. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer\u2019s dementia. Proc Natl Acad Sci USA. 2004;101:284\u20139.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1966_CR15","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/s41582-018-0032-9","volume":"14","author":"MT Ferretti","year":"2018","unstructured":"Ferretti MT, Iulita MF, Cavedo E, Chiesa PA, Schumacher Dimech A, Santuccione, et al. Sex differences in Alzheimer disease - the gateway to precision medicine. Nat Rev Neurol. 2018;14:457\u201369.","journal-title":"Nat Rev Neurol"},{"key":"1966_CR16","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.brainres.2019.05.031","volume":"1719","author":"CA Toro","year":"2019","unstructured":"Toro CA, Zhang L, Cao J, Cai D. Sex differences in Alzheimer\u2019s disease: Understanding the molecular impact. Brain Res. 2019;1719:194\u2013207.","journal-title":"Brain Res"},{"key":"1966_CR17","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/j.mad.2006.05.001","volume":"127","author":"J Tower","year":"2006","unstructured":"Tower J. Sex-specific regulation of aging and apoptosis. Mech Ageing Dev. 2006;127:705\u201318.","journal-title":"Mech Ageing Dev"},{"key":"1966_CR18","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1152\/physrev.1998.78.2.547","volume":"78","author":"KB Beckman","year":"1998","unstructured":"Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev. 1998;78:547\u201381.","journal-title":"Physiol Rev"},{"key":"1966_CR19","doi-asserted-by":"publisher","first-page":"15605","DOI":"10.1073\/pnas.0806883105","volume":"105","author":"NC Berchtold","year":"2008","unstructured":"Berchtold NC, Cribbs DH, Coleman PD, Rogers J, Head E, Kim R, et al. Gene expression changes in the course of normal brain aging are sexually dimorphic. Proc Natl Acad Sci USA. 2008;105:15605\u201310.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1966_CR20","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1056\/NEJM200008173430701","volume":"343","author":"SY Bookheimer","year":"2000","unstructured":"Bookheimer SY, Strojwas MH, Cohen MS, Saunders AM, Pericak-Vance MA, Mazziotta JC, et al. Patterns of brain activation in people at risk for Alzheimer\u2019s disease. N. Engl J Med. 2000;343:450\u20136.","journal-title":"N. Engl J Med"},{"key":"1966_CR21","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/0169-328X(93)90012-E","volume":"17","author":"J Demmer","year":"1993","unstructured":"Demmer J, Dragunow M, Lawlor PA, Mason SE, Leah JD, Abraham WC, et al. Differential expression of immediate early genes after hippocampal long-term potentiation in awake rats. Brain Res Mol Brain Res. 1993;17:279\u201386.","journal-title":"Brain Res Mol Brain Res"},{"key":"1966_CR22","first-page":"78","volume":"8","author":"K Minatohara","year":"2015","unstructured":"Minatohara K, Akiyoshi M, Okuno H. Role of immediate-early genes in synaptic plasticity and neuronal ensembles underlying the memory trace. Front Mol Neurosci. 2015;8:78.","journal-title":"Front Mol Neurosci"},{"key":"1966_CR23","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1038\/340474a0","volume":"340","author":"AJ Cole","year":"1989","unstructured":"Cole AJ, Saffen DW, Baraban JM, Worley PF. Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation. Nature. 1989;340:474\u20136.","journal-title":"Nature"},{"key":"1966_CR24","doi-asserted-by":"publisher","first-page":"5089","DOI":"10.1523\/JNEUROSCI.21-14-05089.2001","volume":"21","author":"JF Guzowski","year":"2001","unstructured":"Guzowski JF, Setlow B, Wagner EK, McGaugh JL. Experience-dependent gene expression in the rat hippocampus after spatial learning: a comparison of the immediate-early genes Arc, c-fos, and zif268. J Neurosci. 2001;21:5089\u201398.","journal-title":"J Neurosci"},{"key":"1966_CR25","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.pharmthera.2012.09.001","volume":"137","author":"S Healy","year":"2013","unstructured":"Healy S, Khan P, Davie JR. Immediate early response genes and cell transformation. Pharm Ther. 2013;137:64\u201377.","journal-title":"Pharm Ther"},{"key":"1966_CR26","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/S0197-0186(98)00023-0","volume":"33","author":"KJ Kovacs","year":"1998","unstructured":"Kovacs KJ. c-Fos as a transcription factor: A stressful (re)view from a functional map. Neurochem Int. 1998;33:287\u201397.","journal-title":"Neurochem Int"},{"key":"1966_CR27","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.neuron.2014.05.018","volume":"83","author":"CA Denny","year":"2014","unstructured":"Denny CA, Kheirbek MA, Alba EL, Tanaka KF, Brachman RA, Laughman KB, et al. Hippocampal memory traces are differentially modulated by experience, time, and adult neurogenesis. Neuron. 2014;83:189\u2013201.","journal-title":"Neuron"},{"key":"1966_CR28","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/nature11028","volume":"484","author":"X Liu","year":"2012","unstructured":"Liu X, Ramirez S, Pang PT, Puryear CB, Govindarajan A, Deisseroth K, et al. Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature. 2012;484:381\u20135.","journal-title":"Nature"},{"key":"1966_CR29","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02256-2","volume":"18","author":"NS Jones","year":"2021","unstructured":"Jones NS, Watson KQ, Rebeck GW. High-fat diet increases gliosis and immediate early gene expression in APOE3 mice, but not APOE4 mice. J Neuroinflammation. 2021;18:214.","journal-title":"J Neuroinflammation"},{"key":"1966_CR30","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.cell.2016.12.044","volume":"168","author":"YA Huang","year":"2017","unstructured":"Huang YA, Zhou B, Wernig M, Sudhof TC. ApoE2. ApoE3, and ApoE4 differentially stimulate APP transcription and abeta secretion. Cell. 2017;168:427\u201341.e421.","journal-title":"Cell"},{"key":"1966_CR31","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1016\/j.cell.2015.05.032","volume":"161","author":"R Madabhushi","year":"2015","unstructured":"Madabhushi R, Gao F, Pfenning AR, Pan L, Yamakawa S, Seo J, et al. Activity-induced dna breaks govern the expression of neuronal early-response genes. Cell. 2015;161:1592\u2013605.","journal-title":"Cell"},{"key":"1966_CR32","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1038\/nn.3356","volume":"16","author":"E Suberbielle","year":"2013","unstructured":"Suberbielle E, Sanchez PE, Kravitz AV, Wang X, Ho K, Eilertson K, et al. Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-beta. Nat Neurosci. 2013;16:613\u201321.","journal-title":"Nat Neurosci"},{"key":"1966_CR33","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s40478-019-0723-5","volume":"7","author":"NM Shanbhag","year":"2019","unstructured":"Shanbhag NM, Evans MD, Mao W, Nana AL, Seeley WW, Adame A, et al. Early neuronal accumulation of DNA double strand breaks in Alzheimer\u2019s disease. Acta Neuropathol Commun. 2019;7:77.","journal-title":"Acta Neuropathol Commun"},{"key":"1966_CR34","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1146\/annurev.neuro.24.1.897","volume":"24","author":"S Maren","year":"2001","unstructured":"Maren S. Neurobiology of Pavlovian fear conditioning. Annu Rev Neurosci. 2001;24:897\u2013931.","journal-title":"Annu Rev Neurosci"},{"key":"1966_CR35","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/S0149-7634(99)00016-0","volume":"23","author":"M Fendt","year":"1999","unstructured":"Fendt M, Fanselow MS. The neuroanatomical and neurochemical basis of conditioned fear. Neurosci Biobehav Rev. 1999;23:743\u201360.","journal-title":"Neurosci Biobehav Rev"},{"key":"1966_CR36","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/nrn3945","volume":"16","author":"P Tovote","year":"2015","unstructured":"Tovote P, Fadok JP, Luthi A. Neuronal circuits for fear and anxiety. Nat Rev Neurosci. 2015;16:317\u201331.","journal-title":"Nat Rev Neurosci"},{"key":"1966_CR37","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.brainresbull.2007.06.006","volume":"74","author":"NM Conejo","year":"2007","unstructured":"Conejo NM, Gonzalez-Pardo H, Lopez M, Cantora R, Arias JL. Induction of c-Fos expression in the mammillary bodies, anterior thalamus and dorsal hippocampus after fear conditioning. Brain Res Bull. 2007;74:172\u20137.","journal-title":"Brain Res Bull"},{"key":"1966_CR38","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1034\/j.1601-183X.2003.00001.x","volume":"2","author":"T Strekalova","year":"2003","unstructured":"Strekalova T, Zorner B, Zacher C, Sadovska G, Herdegen T, Gass P. Memory retrieval after contextual fear conditioning induces c-Fos and JunB expression in CA1 hippocampus. Genes Brain Behav. 2003;2:3\u201310.","journal-title":"Genes Brain Behav"},{"key":"1966_CR39","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.neuron.2014.09.037","volume":"84","author":"KZ Tanaka","year":"2014","unstructured":"Tanaka KZ, Pevzner A, Hamidi AB, Nakazawa Y, Graham J, Wiltgen BJ. Cortical representations are reinstated by the hippocampus during memory retrieval. Neuron. 2014;84:347\u201354.","journal-title":"Neuron"},{"key":"1966_CR40","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1038\/mp.2015.88","volume":"21","author":"MA Fullana","year":"2016","unstructured":"Fullana MA, Harrison BJ, Soriano-Mas C, Vervliet B, Cardoner N, Avila-Parcet A, et al. Neural signatures of human fear conditioning: an updated and extended meta-analysis of fMRI studies. Mol Psychiatry. 2016;21:500\u20138.","journal-title":"Mol Psychiatry"},{"key":"1966_CR41","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1111\/j.1601-183X.2012.00833.x","volume":"11","author":"RH Olsen","year":"2012","unstructured":"Olsen RH, Agam M, Davis MJ, Raber J. ApoE isoform-dependent deficits in extinction of contextual fear conditioning. Genes Brain Behav. 2012;11:806\u201312.","journal-title":"Genes Brain Behav"},{"key":"1966_CR42","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1111\/jnc.13737","volume":"138","author":"LE Villasana","year":"2016","unstructured":"Villasana LE, Weber S, Akinyeke T, Raber J. Genotype differences in anxiety and fear learning and memory of WT and ApoE4 mice associated with enhanced generation of hippocampal reactive oxygen species. J Neurochem. 2016;138:896\u2013908.","journal-title":"J Neurochem"},{"key":"1966_CR43","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.celrep.2014.12.014","volume":"10","author":"Y Kim","year":"2015","unstructured":"Kim Y, Venkataraju KU, Pradhan K, Mende C, Taranda J, Turaga SC, et al. Mapping social behavior-induced brain activation at cellular resolution in the mouse. Cell Rep. 2015;10:292\u2013305.","journal-title":"Cell Rep"},{"key":"1966_CR44","doi-asserted-by":"publisher","first-page":"326","DOI":"10.3389\/fnins.2015.00326","volume":"9","author":"DG Zuloaga","year":"2015","unstructured":"Zuloaga DG, Iancu OD, Weber S, Etzel D, Marzulla T, Stewart B, et al. Enhanced functional connectivity involving the ventromedial hypothalamus following methamphetamine exposure. Front Neurosci. 2015;9:326.","journal-title":"Front Neurosci"},{"key":"1966_CR45","doi-asserted-by":"publisher","first-page":"770502","DOI":"10.3389\/fphys.2021.770502","volume":"12","author":"SW Boutros","year":"2021","unstructured":"Boutros SW, Zimmerman B, Nagy SC, Lee JS, Perez R, Raber J. Amifostine (WR-2721) Mitigates Cognitive Injury Induced by Heavy Ion Radiation in Male Mice and Alters Behavior and Brain Connectivity. Front Physiol. 2021;12:770502.","journal-title":"Front Physiol"},{"key":"1966_CR46","doi-asserted-by":"publisher","first-page":"17972","DOI":"10.1074\/jbc.272.29.17972","volume":"272","author":"PM Sullivan","year":"1997","unstructured":"Sullivan PM, Mezdour H, Aratani Y, Knouff C, Najib J, Reddick RL, et al. Targeted replacement of the mouse apolipoprotein E gene with the common human APOE3 allele enhances diet-induced hypercholesterolemia and atherosclerosis. J Biol Chem. 1997;272:17972\u201380.","journal-title":"J Biol Chem"},{"key":"1966_CR47","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1172\/JCI2673","volume":"102","author":"PM Sullivan","year":"1998","unstructured":"Sullivan PM, Mezdour H, Quarfordt SH, Maeda N. Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting from gene replacement of mouse Apoe with human Apoe*2. J Clin Invest. 1998;102:130\u20135.","journal-title":"J Clin Invest"},{"key":"1966_CR48","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.1172\/JCI6172","volume":"103","author":"C Knouff","year":"1999","unstructured":"Knouff C, Hinsdale ME, Mezdour H, Altenburg MK, Watanabe M, Quarfordt SH, et al. Apo E structure determines VLDL clearance and atherosclerosis risk in mice. J Clin Invest. 1999;103:1579\u201386.","journal-title":"J Clin Invest"},{"key":"1966_CR49","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1111\/jnc.12651","volume":"129","author":"DG Zuloaga","year":"2014","unstructured":"Zuloaga DG, Johnson LA, Agam M, Raber J. Sex differences in activation of the hypothalamic-pituitary-adrenal axis by methamphetamine. J Neurochem. 2014;129:495\u2013508.","journal-title":"J Neurochem"},{"key":"1966_CR50","doi-asserted-by":"publisher","first-page":"9569","DOI":"10.1073\/pnas.86.23.9569","volume":"86","author":"S Ceccatelli","year":"1989","unstructured":"Ceccatelli S, Villar MJ, Goldstein M, Hokfelt T. Expression of c-Fos immunoreactivity in transmitter-characterized neurons after stress. Proc Natl Acad Sci USA. 1989;86:9569\u201373.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1966_CR51","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.dnarep.2018.11.008","volume":"73","author":"M Mirza-Aghazadeh-Attari","year":"2019","unstructured":"Mirza-Aghazadeh-Attari M, Mohammadzadeh A, Yousefi B, Mihanfar A, Karimian A, Majidinia M. 53BP1: A key player of DNA damage response with critical functions in cancer. DNA Repair (Amst). 2019;73:110\u20139.","journal-title":"DNA Repair (Amst)"},{"key":"1966_CR52","doi-asserted-by":"crossref","unstructured":"Navabpour S, Rogers J, McFadden T, Jarome TJ. DNA Double-Strand Breaks Are a Critical Regulator of Fear Memory Reconsolidation. Int J Mol Sci. 2020;21:8995\u20139009.","DOI":"10.3390\/ijms21238995"},{"key":"1966_CR53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bbr.2015.10.050","volume":"298","author":"T Kugelman","year":"2016","unstructured":"Kugelman T, Zuloaga DG, Weber S, Raber J. Post-training gamma irradiation-enhanced contextual fear memory associated with reduced neuronal activation of the infralimbic cortex. Behav Brain Res. 2016;298:1\u201311.","journal-title":"Behav Brain Res"},{"key":"1966_CR54","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-47227-z","volume":"9","author":"AJ Schaser","year":"2019","unstructured":"Schaser AJ, Osterberg VR, Dent SE, Stackhouse TL, Wakeham CM, Boutros SW, et al. Alpha-synuclein is a DNA binding protein that modulates DNA repair with implications for Lewy body disorders. Sci Rep. 2019;9:10919.","journal-title":"Sci Rep."},{"key":"1966_CR55","doi-asserted-by":"publisher","first-page":"3972","DOI":"10.1093\/molbev\/msab148","volume":"38","author":"GA Hartley","year":"2021","unstructured":"Hartley GA, Okhovat M, O\u2019Neill RJ, Carbone L. Comparative Analyses of Gibbon Centromeres Reveal Dynamic Genus-Specific Shifts in Repeat Composition. Mol Biol Evol. 2021;38:3972\u201392.","journal-title":"Mol Biol Evol"},{"key":"1966_CR56","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02217-x","volume":"7","author":"SC Taylor","year":"2017","unstructured":"Taylor SC, Laperriere G, Germain H. Droplet Digital PCR versus qPCR for gene expression analysis with low abundant targets: from variable nonsense to publication quality data. Sci Rep. 2017;7:2409.","journal-title":"Sci Rep."},{"key":"1966_CR57","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1016\/j.cell.2016.05.007","volume":"165","author":"N Renier","year":"2016","unstructured":"Renier N, Adams EL, Kirst C, Wu Z, Azevedo R, Kohl J, et al. Mapping of brain activity by automated volume analysis of immediate early genes. Cell. 2016;165:1789\u2013802.","journal-title":"Cell"},{"key":"1966_CR58","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1111\/biom.12552","volume":"73","author":"J Chang","year":"2017","unstructured":"Chang J, Zhou W, Zhou WX, Wang L. Comparing large covariance matrices under weak conditions on the dependence structure and its application to gene clustering. Biometrics. 2017;73:31\u201341.","journal-title":"Biometrics"},{"key":"1966_CR59","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1080\/01621459.2020.1738234","volume":"116","author":"KZ Lin","year":"2021","unstructured":"Lin KZ, Liu H, Roeder K. Covariance-based sample selection for heterogeneous data: Applications to gene expression and autism risk gene detection. J Am Stat Assoc. 2021;116:54\u201367.","journal-title":"J Am Stat Assoc"},{"key":"1966_CR60","doi-asserted-by":"publisher","first-page":"2786","DOI":"10.1214\/13-AOS1161","volume":"41","author":"V Chernozhukov","year":"2013","unstructured":"Chernozhukov V, Chetverikov D, Kato K. Gaussian approximations and multiplier bootstrap for maxima of sums of high-dimensional random vectors. Ann Stat. 2013;41:2786\u2013819.","journal-title":"Ann Stat"},{"key":"1966_CR61","doi-asserted-by":"publisher","first-page":"767558","DOI":"10.3389\/fnagi.2022.767558","volume":"14","author":"S Holden","year":"2022","unstructured":"Holden S, Kundu P, Torres ERS, Sudhakar R, Krenik D, Grygoryev D, et al. Apolipoprotein E Isoform-Dependent Effects on Human Amyloid Precursor Protein\/Abeta-Induced Behavioral Alterations and Cognitive Impairments and Insoluble Cortical Abeta42 Levels. Front Aging Neurosci. 2022;14:767558.","journal-title":"Front Aging Neurosci"},{"key":"1966_CR62","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1111\/j.1474-9726.2011.00705.x","volume":"10","author":"J Deelen","year":"2011","unstructured":"Deelen J, Beekman M, Uh HW, Helmer Q, Kuningas M, Christiansen L, et al. Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited. Aging Cell. 2011;10:686\u201398.","journal-title":"Aging Cell"},{"key":"1966_CR63","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.mad.2011.06.008","volume":"132","author":"A Nebel","year":"2011","unstructured":"Nebel A, Kleindorp R, Caliebe A, Nothnagel M, Blanche H, Junge O, et al. A genome-wide association study confirms APOE as the major gene influencing survival in long-lived individuals. Mech Ageing Dev. 2011;132:324\u201330.","journal-title":"Mech Ageing Dev"},{"key":"1966_CR64","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s13024-020-00413-4","volume":"15","author":"Z Li","year":"2020","unstructured":"Li Z, Shue F, Zhao N, Shinohara M, Bu G. APOE2: protective mechanism and therapeutic implications for Alzheimer\u2019s disease. Mol Neurodegener. 2020;15:63.","journal-title":"Mol Neurodegener"},{"key":"1966_CR65","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14279-8","volume":"11","author":"EM Reiman","year":"2020","unstructured":"Reiman EM, Arboleda-Velasquez JF, Quiroz YT, Huentelman MJ, Beach TG, Caselli RJ, et al. Exceptionally low likelihood of Alzheimer\u2019s dementia in APOE2 homozygotes from a 5,000-person neuropathological study. Nat Commun. 2020;11:667.","journal-title":"Nat Commun"},{"key":"1966_CR66","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1037\/pas0000486","volume":"30","author":"FW Weathers","year":"2018","unstructured":"Weathers FW, Bovin MJ, Lee DJ, Sloan DM, Schnurr PP, Kaloupek DG, et al. The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5): Development and initial psychometric evaluation in military veterans. Psychol Assess. 2018;30:383\u201395.","journal-title":"Psychol Assess"},{"key":"1966_CR67","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1002\/da.22348","volume":"32","author":"NA Kimbrel","year":"2015","unstructured":"Kimbrel NA, Hauser MA, Garrett M, Ashley-Koch A, Liu Y, Dennis MF, et al. EFFECT OF THE APOE epsilon4 ALLELE AND COMBAT EXPOSURE ON PTSD AMONG IRAQ\/AFGHANISTAN-ERA VETERANS. Depress Anxiety. 2015;32:307\u201315.","journal-title":"Depress Anxiety"},{"key":"1966_CR68","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1017\/S0033291796004229","volume":"27","author":"JR Davidson","year":"1997","unstructured":"Davidson JR, Book SW, Colket JT, Tupler LA, Roth S, David D, et al. Assessment of a new self-rating scale for post-traumatic stress disorder. Psychol Med. 1997;27:153\u201360.","journal-title":"Psychol Med"},{"key":"1966_CR69","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/S0165-1781(99)00070-0","volume":"88","author":"S Meltzer-Brody","year":"1999","unstructured":"Meltzer-Brody S, Churchill E, Davidson JR. Derivation of the SPAN, a brief diagnostic screening test for post-traumatic stress disorder. Psychiatry Res. 1999;88:63\u201370.","journal-title":"Psychiatry Res"},{"key":"1966_CR70","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.janxdis.2008.07.007","volume":"23","author":"SD McDonald","year":"2009","unstructured":"McDonald SD, Beckham JC, Morey RA, Calhoun PS. The validity and diagnostic efficiency of the Davidson Trauma Scale in military veterans who have served since September 11th, 2001. J Anxiety Disord. 2009;23:247\u201355.","journal-title":"J Anxiety Disord"},{"key":"1966_CR71","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1212\/WNL.45.3.555","volume":"45","author":"R Mayeux","year":"1995","unstructured":"Mayeux R, Ottman R, Maestre G, Ngai C, Tang MX, Ginsberg H, et al. Synergistic effects of traumatic head injury and apolipoprotein-epsilon 4 in patients with Alzheimer\u2019s disease. Neurology. 1995;45:555\u20137.","journal-title":"Neurology"},{"key":"1966_CR72","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/jcbfm.2015.44","volume":"36","author":"MR Halliday","year":"2016","unstructured":"Halliday MR, Rege SV, Ma Q, Zhao Z, Miller CA, Winkler EA, et al. Accelerated pericyte degeneration and blood\u2013brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer\u2019s disease. J Cereb Blood Flow Metab. 2016;36:216\u201327.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1966_CR73","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-11654-7","volume":"7","author":"J Cao","year":"2017","unstructured":"Cao J, Gaamouch FE, Meabon JS, Meeker KD, Zhu L, Zhong MB, et al. ApoE4-associated phospholipid dysregulation contributes to development of Tau hyper-phosphorylation after traumatic brain injury. Sci Rep. 2017;7:11372.","journal-title":"Sci Rep"},{"key":"1966_CR74","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-76849-x","volume":"10","author":"AO Giarratana","year":"2020","unstructured":"Giarratana AO, Zheng C, Reddi S, Teng SL, Berger D, Adler D, et al. APOE4 genetic polymorphism results in impaired recovery in a repeated mild traumatic brain injury model and treatment with Bryostatin-1 improves outcomes. Sci Rep. 2020;10:19919.","journal-title":"Sci Rep"},{"key":"1966_CR75","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1093\/jnen\/nlw049","volume":"75","author":"PM Washington","year":"2016","unstructured":"Washington PM, Burns MP. The Effect of the APOE4 gene on accumulation of abeta40 after brain injury cannot be reversed by increasing apoE4 Protein. J Neuropathol Exp Neurol. 2016;75:770\u20138.","journal-title":"J Neuropathol Exp Neurol"},{"key":"1966_CR76","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.jagp.2019.08.006","volume":"28","author":"P Desmarais","year":"2020","unstructured":"Desmarais P, Weidman D, Wassef A, Bruneau M-A, Friedland J, Bajsarowicz P, et al. The interplay between post-traumatic stress disorder and dementia: a systematic review. Am J Geriatr Psychiatry. 2020;28:48\u201360.","journal-title":"Am J Geriatr Psychiatry"},{"key":"1966_CR77","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/mp.2009.117","volume":"16","author":"SM Kurian","year":"2011","unstructured":"Kurian SM, Le-Niculescu H, Patel SD, Bertram D, Davis J, Dike C, et al. Identification of blood biomarkers for psychosis using convergent functional genomics. Mol Psychiatry. 2011;16:37\u201358.","journal-title":"Mol Psychiatry"},{"key":"1966_CR78","doi-asserted-by":"publisher","first-page":"e0116686","DOI":"10.1371\/journal.pone.0116686","volume":"10","author":"N Cattane","year":"2015","unstructured":"Cattane N, Minelli A, Milanesi E, Maj C, Bignotti S, Bortolomasi M, et al. Altered gene expression in schizophrenia: findings from transcriptional signatures in fibroblasts and blood. PLoS One. 2015;10:e0116686.","journal-title":"PLoS One"},{"key":"1966_CR79","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.jad.2011.10.023","volume":"140","author":"RS Lee","year":"2012","unstructured":"Lee RS, Hermens DF, Porter MA, Redoblado-Hodge MA. A meta-analysis of cognitive deficits in first-episode Major Depressive Disorder. J Affect Disord. 2012;140:113\u201324.","journal-title":"J Affect Disord"},{"key":"1966_CR80","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.1111\/j.1460-9568.2010.07242.x","volume":"31","author":"S Ons","year":"2010","unstructured":"Ons S, Rotllant D, Marin-Blasco IJ, Armario A. Immediate-early gene response to repeated immobilization: Fos protein and arc mRNA levels appear to be less sensitive than c-fos mRNA to adaptation. Eur J Neurosci. 2010;31:2043\u201352.","journal-title":"Eur J Neurosci"},{"key":"1966_CR81","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/0306-4522(92)90004-L","volume":"46","author":"P Zhang","year":"1992","unstructured":"Zhang P, Hirsch EC, Damier P, Duyckaerts C, Javoy-Agid F. c-fos protein-like immunoreactivity: distribution in the human brain and over-expression in the hippocampus of patients with Alzheimer\u2019s disease. Neuroscience. 1992;46:9\u201321.","journal-title":"Neuroscience"},{"key":"1966_CR82","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1006\/exnr.1994.1031","volume":"125","author":"AJ Anderson","year":"1994","unstructured":"Anderson AJ, Cummings BJ, Cotman CW. Increased immunoreactivity for Jun- and Fos-related proteins in Alzheimer\u2019s disease: association with pathology. Exp Neurol. 1994;125:286\u201395.","journal-title":"Exp Neurol"},{"key":"1966_CR83","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/S0197-4580(98)00077-3","volume":"19","author":"DL Marcus","year":"1998","unstructured":"Marcus DL, Strafaci JA, Miller DC, Masia S, Thomas CG, Rosman J, et al. Quantitative neuronal c-fos and c-jun expression in Alzheimer\u2019s disease. Neurobiol Aging. 1998;19:393\u2013400.","journal-title":"Neurobiol Aging"},{"key":"1966_CR84","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.celrep.2017.06.040","volume":"20","author":"BF Corbett","year":"2017","unstructured":"Corbett BF, You JC, Zhang X, Pyfer MS, Tosi U, Iascone DM, et al. DeltaFosB Regulates Gene Expression and Cognitive Dysfunction in a Mouse Model of Alzheimer\u2019s Disease. Cell Rep. 2017;20:344\u201355.","journal-title":"Cell Rep"},{"key":"1966_CR85","doi-asserted-by":"publisher","first-page":"e99467","DOI":"10.1371\/journal.pone.0099467","volume":"9","author":"A Hendrickx","year":"2014","unstructured":"Hendrickx A, Pierrot N, Tasiaux B, Schakman O, Kienlen-Campard P, De Smet C, et al. Epigenetic regulations of immediate early genes expression involved in memory formation by the amyloid precursor protein of Alzheimer disease. PLoS One. 2014;9:e99467.","journal-title":"PLoS One"},{"key":"1966_CR86","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/1423-0127-17-29","volume":"17","author":"JC Kung","year":"2010","unstructured":"Kung JC, Chen TC, Shyu BC, Hsiao S, Huang AC. Anxiety- and depressive-like responses and c-fos activity in preproenkephalin knockout mice: oversensitivity hypothesis of enkephalin deficit-induced posttraumatic stress disorder. J Biomed Sci. 2010;17:29.","journal-title":"J Biomed Sci"},{"key":"1966_CR87","doi-asserted-by":"publisher","first-page":"100226","DOI":"10.1016\/j.ynstr.2020.100226","volume":"13","author":"H Azevedo","year":"2020","unstructured":"Azevedo H, Ferreira M, Mascarello A, Osten P, Guimaraes CRW. Brain-wide mapping of c-fos expression in the single prolonged stress model and the effects of pretreatment with ACH-000029 or prazosin. Neurobiol Stress. 2020;13:100226.","journal-title":"Neurobiol Stress"},{"key":"1966_CR88","doi-asserted-by":"publisher","first-page":"7408","DOI":"10.1523\/JNEUROSCI.2994-18.2019","volume":"39","author":"YA Huang","year":"2019","unstructured":"Huang YA, Zhou B, Nabet AM, Wernig M, Sudhof TC. Differential Signaling Mediated by ApoE2, ApoE3, and ApoE4 in Human Neurons Parallels Alzheimer\u2019s Disease Risk. J Neurosci. 2019;39:7408\u201327.","journal-title":"J Neurosci"},{"key":"1966_CR89","doi-asserted-by":"publisher","first-page":"11445","DOI":"10.1523\/JNEUROSCI.1972-08.2008","volume":"28","author":"DR Riddell","year":"2008","unstructured":"Riddell DR, Zhou H, Atchison K, Warwick HK, Atkinson PJ, Jefferson J, et al. Impact of apolipoprotein E (ApoE) polymorphism on brain ApoE levels. J Neurosci. 2008;28:11445\u201353.","journal-title":"J Neurosci"},{"key":"1966_CR90","doi-asserted-by":"publisher","first-page":"10658","DOI":"10.1523\/JNEUROSCI.1922-05.2005","volume":"25","author":"G Ramaswamy","year":"2005","unstructured":"Ramaswamy G, Xu Q, Huang Y, Weisgraber KH. Effect of domain interaction on apolipoprotein E levels in mouse brain. J Neurosci. 2005;25:10658\u201363.","journal-title":"J Neurosci"},{"key":"1966_CR91","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.euprot.2015.07.012","volume":"8","author":"M Rezeli","year":"2015","unstructured":"Rezeli M, Zetterberg H, Blennow K, Brinkmalm A, sLaurell T, Hansson O, et al. Quantification of total apolipoprotein E and its specific isoforms in cerebrospinal fluid and blood in Alzheimer\u2019s disease and other neurodegenerative diseases. EuPA Open Proteom. 2015;8:137\u201343.","journal-title":"EuPA Open Proteom"},{"key":"1966_CR92","doi-asserted-by":"publisher","first-page":"349","DOI":"10.3389\/fnhum.2016.00349","volume":"10","author":"K Konishi","year":"2016","unstructured":"Konishi K, Bhat V, Banner H, Poirier J, Joober R, Bohbot VD. APOE2 Is Associated with Spatial Navigational Strategies and Increased Gray Matter in the Hippocampus. Front Hum Neurosci. 2016;10:349.","journal-title":"Front Hum Neurosci"},{"key":"1966_CR93","doi-asserted-by":"publisher","first-page":"58789","DOI":"10.18632\/oncotarget.11289","volume":"7","author":"J Chen","year":"2016","unstructured":"Chen J, Shu H, Wang Z, Liu D, Shi Y, Xu L, et al. Protective effect of APOE epsilon 2 on intrinsic functional connectivity of the entorhinal cortex is associated with better episodic memory in elderly individuals with risk factors for Alzheimer\u2019s disease. Oncotarget. 2016;7:58789\u2013801.","journal-title":"Oncotarget"},{"key":"1966_CR94","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1016\/j.neurobiolaging.2005.03.009","volume":"27","author":"DA Shackelford","year":"2006","unstructured":"Shackelford DA. DNA end joining activity is reduced in Alzheimer\u2019s disease. Neurobiol Aging. 2006;27:596\u2013605.","journal-title":"Neurobiol Aging"},{"key":"1966_CR95","doi-asserted-by":"publisher","first-page":"e99897","DOI":"10.1371\/journal.pone.0099897","volume":"9","author":"AR Silva","year":"2014","unstructured":"Silva AR, Santos AC, Farfel JM, Grinberg LT, Ferretti RE, Campos AH, et al. Repair of oxidative DNA damage, cell-cycle regulation and neuronal death may influence the clinical manifestation of Alzheimer\u2019s disease. PLoS One. 2014;9:e99897.","journal-title":"PLoS One"},{"key":"1966_CR96","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1038\/nature02661","volume":"429","author":"T Lu","year":"2004","unstructured":"Lu T, Pan Y, Kao SY, Li C, Kohane I, Chan J, et al. Gene regulation and DNA damage in the ageing human brain. Nature. 2004;429:883\u201391.","journal-title":"Nature"},{"key":"1966_CR97","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.molbrainres.2004.05.023","volume":"128","author":"E Jacobsen","year":"2004","unstructured":"Jacobsen E, Beach T, Shen Y, Li R, Chang Y. Deficiency of the Mre11 DNA repair complex in Alzheimer\u2019s disease brains. Brain Res Mol Brain Res. 2004;128:1\u20137.","journal-title":"Brain Res Mol Brain Res"},{"key":"1966_CR98","doi-asserted-by":"publisher","first-page":"24872","DOI":"10.18632\/aging.202419","volume":"12","author":"T Anglada","year":"2020","unstructured":"Anglada T, Genesca A, Martin M. Age-associated deficient recruitment of 53BP1 in G1 cells directs DNA double-strand break repair to BRCA1\/CtIP-mediated DNA-end resection. Aging (Albany NY). 2020;12:24872\u201393.","journal-title":"Aging (Albany NY)"},{"key":"1966_CR99","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1001\/jamaneurol.2017.2188","volume":"74","author":"SC Neu","year":"2017","unstructured":"Neu SC, Pa J, Kukull W, Beekly D, Kuzma A, Gangadharan P, et al. Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease: A Meta-analysis. JAMA Neurol. 2017;74:1178\u201389.","journal-title":"JAMA Neurol"},{"key":"1966_CR100","doi-asserted-by":"publisher","first-page":"e0249691.","DOI":"10.1371\/journal.pone.0249691","volume":"16","author":"RT Stott","year":"2021","unstructured":"Stott RT, Kritsky O, Tsai LH. Profiling DNA break sites and transcriptional changes in response to contextual fear learning. PLoS One. 2021;16:e0249691.","journal-title":"PLoS One"},{"key":"1966_CR101","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23644-4","volume":"8","author":"H Yu","year":"2018","unstructured":"Yu H, Harrison FE, Xia F. Altered DNA repair; an early pathogenic pathway in Alzheimer\u2019s disease and obesity. Sci Rep. 2018;8:5600.","journal-title":"Sci Rep"}],"container-title":["Molecular Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41380-023-01966-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-023-01966-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-023-01966-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T16:04:48Z","timestamp":1698854688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41380-023-01966-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,2]]},"references-count":101,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["1966"],"URL":"https:\/\/doi.org\/10.1038\/s41380-023-01966-8","relation":{},"ISSN":["1359-4184","1476-5578"],"issn-type":[{"value":"1359-4184","type":"print"},{"value":"1476-5578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,2]]},"assertion":[{"value":"19 April 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2023","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2023","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 February 2023","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}