{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T11:39:35Z","timestamp":1792582775186,"version":"4.5.0"},"reference-count":110,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T00:00:00Z","timestamp":1705536000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS093482"],"award-info":[{"award-number":["NS093482"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS110719"],"award-info":[{"award-number":["NS110719"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS117469"],"award-info":[{"award-number":["NS117469"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD076892"],"award-info":[{"award-number":["HD076892"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG10161"],"award-info":[{"award-number":["P30AG10161"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG72975"],"award-info":[{"award-number":["P30AG72975"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG15819"],"award-info":[{"award-number":["R01AG15819"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG17917"],"award-info":[{"award-number":["R01AG17917"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG036836"],"award-info":[{"award-number":["R01AG036836"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U01AG46152"],"award-info":[{"award-number":["U01AG46152"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U01AG61356"],"award-info":[{"award-number":["U01AG61356"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U01AG046139"],"award-info":[{"award-number":["U01AG046139"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P50 AG016574"],"award-info":[{"award-number":["P50 AG016574"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG032990"],"award-info":[{"award-number":["R01 AG032990"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG018023"],"award-info":[{"award-number":["R01AG018023"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U01AG006576"],"award-info":[{"award-number":["U01AG006576"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U01AG006786"],"award-info":[{"award-number":["U01AG006786"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG025711"],"award-info":[{"award-number":["R01AG025711"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG017216"],"award-info":[{"award-number":["R01AG017216"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG003949"],"award-info":[{"award-number":["R01AG003949"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS080820"],"award-info":[{"award-number":["R01NS080820"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U24NS072026"],"award-info":[{"award-number":["U24NS072026"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG19610"],"award-info":[{"award-number":["P30AG19610"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U01AG046170"],"award-info":[{"award-number":["U01AG046170"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["RF1AG057440"],"award-info":[{"award-number":["RF1AG057440"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U24AG061340"],"award-info":[{"award-number":["U24AG061340"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a complex neurodegenerative disorder with both genetic and non-genetic causes. Animal research models are available for a multitude of diseases and conditions affecting the central nervous system (CNS), and large-scale CNS gene expression data exist for many of these. Although there are several models specifically for AD, each recapitulates different aspects of the human disease. In this study we evaluate over 500 animal models to identify those with CNS gene expression patterns matching human AD datasets. Approaches included a hypergeometric based scoring system that rewards congruent gene expression patterns but penalizes discordant gene expression patterns. The top two models identified were APP\/PS1 transgenic mice expressing mutant APP and PSEN1, and mice carrying a GFAP mutation that is causative of Alexander disease, a primary disorder of astrocytes in the CNS. The APP\/PS1 and GFAP models both matched over 500 genes moving in the same direction as in human AD, and both had elevated GFAP expression and were highly congruent with one another. Also scoring highly were the 5XFAD model (with five mutations in APP and PSEN1) and mice carrying CK-p25, APP, and MAPT mutations. Animals with the APOE3 and 4 mutations combined with traumatic brain injury ranked highly. Bulbectomized rats scored high, suggesting anosmia could be causative of AD-like gene expression. Other matching models included the SOD1G93A strain and knockouts for SNORD116 (Prader-Willi mutation), GRID2, INSM1, XBP1, and CSTB. Many top models demonstrated increased expression of GFAP, and results were similar across multiple human AD datasets. Heatmap and Uniform Manifold Approximation Plot results were consistent with hypergeometric ranking. Finally, some gene manipulation models, including for TYROBP and ATG7, were identified with reversed AD patterns, suggesting possible neuroprotective effects. This study provides insight for the pathobiology of AD and the potential utility of available animal models.<\/jats:p>","DOI":"10.1371\/journal.pone.0291995","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T18:29:06Z","timestamp":1705602546000},"page":"e0291995","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Large-scale gene expression changes in APP\/PSEN1 and GFAP mutation models exhibit high congruence with Alzheimer\u2019s disease"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1341-6094","authenticated-orcid":true,"given":"Stephen C.","family":"Gammie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albee","family":"Messing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mason A.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia A.","family":"Kelm-Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy L.","family":"Hagemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,1,18]]},"reference":[{"issue":"1","key":"pone.0291995.ref001","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/ene.13439","article-title":"Alzheimer\u2019s disease","volume":"25","author":"CA Lane","year":"2018","journal-title":"European Journal of Neurology"},{"issue":"2","key":"pone.0291995.ref002","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.pharep.2014.09.004","article-title":"A review on Alzheimer\u2019s disease pathophysiology and its management: an update","volume":"67","author":"A Kumar","year":"2015","journal-title":"Pharmacological Reports"},{"issue":"1","key":"pone.0291995.ref003","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s13073-016-0355-3","article-title":"Integrative network analysis of nineteen brain regions identifies molecular signatures and networks underlying selective regional vulnerability to Alzheimer\u2019s disease","volume":"8","author":"M Wang","year":"2016","journal-title":"Genome Med"},{"issue":"10","key":"pone.0291995.ref004","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1038\/s41593-018-0236-8","article-title":"Animal models of neurodegenerative diseases","volume":"21","author":"TM Dawson","year":"2018","journal-title":"Nature neuroscience"},{"issue":"4","key":"pone.0291995.ref005","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/ejn.14300","article-title":"Genetically engineered animal models of Parkinson\u2019s disease: From worm to rodent","volume":"49","author":"LS Breger","year":"2019","journal-title":"European Journal of Neuroscience"},{"issue":"10","key":"pone.0291995.ref006","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1038\/nn.2647","article-title":"Animal models of neuropsychiatric disorders","volume":"13","author":"EJ Nestler","year":"2010","journal-title":"Nature neuroscience"},{"issue":"2","key":"pone.0291995.ref007","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s00401-016-1662-x","article-title":"Alzheimer\u2019s disease: experimental models and reality","volume":"133","author":"E Drummond","year":"2017","journal-title":"Acta Neuropathologica"},{"issue":"1","key":"pone.0291995.ref008","doi-asserted-by":"crossref","first-page":"32","DOI":"10.15252\/emmm.201707825","article-title":"The diphenylpyrazole compound anle138b blocks A\u03b2 channels and rescues disease phenotypes in a mouse model for amyloid pathology","volume":"10","author":"A Martinez Hernandez","year":"2018","journal-title":"EMBO Mol Med"},{"issue":"1","key":"pone.0291995.ref009","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/s41591-018-0223-3","article-title":"Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia","volume":"25","author":"V Swarup","year":"2019","journal-title":"Nat Med"},{"issue":"9","key":"pone.0291995.ref010","doi-asserted-by":"crossref","first-page":"3572","DOI":"10.1172\/JCI79942","article-title":"HDAC inhibitor-dependent transcriptome and memory reinstatement in cognitive decline models","volume":"125","author":"E Benito","year":"2015","journal-title":"J Clin Invest"},{"issue":"6","key":"pone.0291995.ref011","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1016\/j.neurobiolaging.2012.11.024","article-title":"Synaptic genes are extensively downregulated across multiple brain regions in normal human aging and Alzheimer\u2019s disease","volume":"34","author":"NC Berchtold","year":"2013","journal-title":"Neurobiol Aging"},{"issue":"2","key":"pone.0291995.ref012","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1152\/physiolgenomics.00242.2007","article-title":"Altered neuronal gene expression in brain regions differentially affected by Alzheimer\u2019s disease: a reference data set","volume":"33","author":"WS Liang","year":"2008","journal-title":"Physiol Genomics"},{"issue":"3","key":"pone.0291995.ref013","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.cell.2013.03.030","article-title":"Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer\u2019s disease","volume":"153","author":"B Zhang","year":"2013","journal-title":"Cell"},{"issue":"7","key":"pone.0291995.ref014","doi-asserted-by":"crossref","first-page":"743","DOI":"10.15252\/msb.20145304","article-title":"Common dysregulation network in the human prefrontal cortex underlies two neurodegenerative diseases","volume":"10","author":"M Narayanan","year":"2014","journal-title":"Mol Syst Biol"},{"issue":"1","key":"pone.0291995.ref015","doi-asserted-by":"crossref","first-page":"17189","DOI":"10.1038\/s41598-022-22179-z","article-title":"Alzheimer\u2019s Disease Large-scale Gene Expression Portrait Identifies Exercise as the Top Theoretical Treatment","volume":"12","author":"MA Hill","year":"2022","journal-title":"Sci Rep"},{"key":"pone.0291995.ref016","doi-asserted-by":"crossref","first-page":"735611","DOI":"10.3389\/fnagi.2021.735611","article-title":"Sex-Specific Cross Tissue Meta-Analysis Identifies Immune Dysregulation in Women With Alzheimer\u2019s Disease","volume":"13","author":"MD Paranjpe","year":"2021","journal-title":"Front Aging Neurosci"},{"key":"pone.0291995.ref017","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3389\/fnins.2020.00209","article-title":"A Systematic Bioinformatics Workflow With Meta-Analytics Identified Potential Pathogenic Factors of Alzheimer\u2019s Disease","volume":"14","author":"SC Yuen","year":"2020","journal-title":"Front Neurosci"},{"issue":"2","key":"pone.0291995.ref018","doi-asserted-by":"crossref","first-page":"107908","DOI":"10.1016\/j.celrep.2020.107908","article-title":"Meta-analysis of the Alzheimer\u2019s disease human brain transcriptome and functional dissection in mouse models","volume":"32","author":"Y-W Wan","year":"2020","journal-title":"Cell reports"},{"issue":"2","key":"pone.0291995.ref019","doi-asserted-by":"crossref","first-page":"eabb5398","DOI":"10.1126\/sciadv.abb5398","article-title":"Molecular subtyping of Alzheimer\u2019s disease using RNA sequencing data reveals novel mechanisms and targets","volume":"7","author":"RA Neff","year":"2021","journal-title":"Science advances"},{"issue":"1","key":"pone.0291995.ref020","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/83679","article-title":"Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease","volume":"27","author":"M Brenner","year":"2001","journal-title":"Nat Genet"},{"issue":"5","key":"pone.0291995.ref021","first-page":"e00109","article-title":"GFAP expression as an indicator of disease severity in mouse models of Alexander disease","author":"PL Jany","year":"2013","journal-title":"ASN Neuro"},{"issue":"15","key":"pone.0291995.ref022","doi-asserted-by":"crossref","first-page":"5017","DOI":"10.1523\/JNEUROSCI.5384-11.2012","article-title":"Alexander disease","volume":"32","author":"A Messing","year":"2012","journal-title":"Journal of Neuroscience"},{"issue":"43","key":"pone.0291995.ref023","doi-asserted-by":"crossref","first-page":"11162","DOI":"10.1523\/JNEUROSCI.3260-06.2006","article-title":"Alexander disease-associated glial fibrillary acidic protein mutations in mice induce Rosenthal fiber formation and a white matter stress response","volume":"26","author":"TL Hagemann","year":"2006","journal-title":"Journal of Neuroscience"},{"issue":"47","key":"pone.0291995.ref024","doi-asserted-by":"crossref","first-page":"18698","DOI":"10.1523\/JNEUROSCI.3693-13.2013","article-title":"Deficits in adult neurogenesis, contextual fear conditioning, and spatial learning in a Gfap mutant mouse model of Alexander disease","volume":"33","author":"TL Hagemann","year":"2013","journal-title":"Journal of Neuroscience"},{"issue":"1","key":"pone.0291995.ref025","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/s41598-021-04020-1","article-title":"Evaluation of animal model congruence to human depression based on large-scale gene expression patterns of the CNS","volume":"12","author":"SC Gammie","year":"2022","journal-title":"Sci Rep"},{"issue":"17","key":"pone.0291995.ref026","doi-asserted-by":"crossref","first-page":"e169","DOI":"10.1093\/nar\/gkq636","article-title":"Rank\u2013rank hypergeometric overlap: identification of statistically significant overlap between gene-expression signatures","volume":"38","author":"SB Plaisier","year":"2010","journal-title":"Nucleic Acids Research"},{"issue":"29","key":"pone.0291995.ref027","doi-asserted-by":"crossref","first-page":"861","DOI":"10.21105\/joss.00861","article-title":"UMAP: Uniform Manifold Approximation and Projection","volume":"3","author":"L McInnes","year":"2018","journal-title":"Journal of Open Source Software"},{"issue":"8","key":"pone.0291995.ref028","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","article-title":"ShinyGO: a graphical gene-set enrichment tool for animals and plants","volume":"36","author":"SX Ge","year":"2020","journal-title":"Bioinformatics"},{"issue":"D1","key":"pone.0291995.ref029","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: protein\u2013protein interaction networks, integrated over the tree of life","volume":"43","author":"D Szklarczyk","year":"2014","journal-title":"Nucleic Acids Research"},{"issue":"11","key":"pone.0291995.ref030","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"P Shannon","year":"2003","journal-title":"Genome research"},{"issue":"3","key":"pone.0291995.ref031","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.neuron.2018.11.040","article-title":"Harnessing genetic complexity to enhance translatability of Alzheimer\u2019s disease mouse models: a path toward precision medicine","volume":"101","author":"SM Neuner","year":"2019","journal-title":"Neuron"},{"key":"pone.0291995.ref032","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2017.05.006","article-title":"Gene co-expression networks identify Trem2 and Tyrobp as major hubs in human APOE expressing mice following traumatic brain injury","volume":"105","author":"EL Castranio","year":"2017","journal-title":"Neurobiol Dis"},{"issue":"28","key":"pone.0291995.ref033","doi-asserted-by":"crossref","first-page":"7906","DOI":"10.1073\/pnas.1603111113","article-title":"Epigenetics and energetics in ventral hippocampus mediate rapid antidepressant action: Implications for treatment resistance","volume":"113","author":"B Bigio","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"39","key":"pone.0291995.ref034","doi-asserted-by":"crossref","first-page":"E8294","DOI":"10.1073\/pnas.1704294114","article-title":"Distinct roles for motor neuron autophagy early and late in the SOD1(G93A) mouse model of ALS","volume":"114","author":"ND Rudnick","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7539","key":"pone.0291995.ref035","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/nature14252","article-title":"Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer\u2019s disease","volume":"518","author":"E Gjoneska","year":"2015","journal-title":"Nature"},{"issue":"16","key":"pone.0291995.ref036","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1093\/hmg\/ddi248","article-title":"Gene expression analysis in mice with elevated glial fibrillary acidic protein and Rosenthal fibers reveals a stress response followed by glial activation and neuronal dysfunction","volume":"14","author":"TL Hagemann","year":"2005","journal-title":"Hum Mol Genet"},{"issue":"4","key":"pone.0291995.ref037","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/nn.2779","article-title":"Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43","volume":"14","author":"M Polymenidou","year":"2011","journal-title":"Nat Neurosci"},{"issue":"1","key":"pone.0291995.ref038","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s40478-017-0431-y","article-title":"Altered Ca(2+) homeostasis induces Calpain-Cathepsin axis activation in sporadic Creutzfeldt-Jakob disease","volume":"5","author":"F Llorens","year":"2017","journal-title":"Acta Neuropathol Commun"},{"issue":"6","key":"pone.0291995.ref039","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/j.1601-183X.2008.00402.x","article-title":"Gene expression patterns in brain cortex of three different animal models of depression","volume":"7","author":"L Urig\u00fcen","year":"2008","journal-title":"Genes Brain Behav"},{"issue":"1","key":"pone.0291995.ref040","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/s41467-017-00922-9","article-title":"LSD1 protects against hippocampal and cortical neurodegeneration","volume":"8","author":"MA Christopher","year":"2017","journal-title":"Nat Commun"},{"issue":"12","key":"pone.0291995.ref041","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.137495","article-title":"Loss of Snord116 impacts lateral hypothalamus, sleep, and food-related behaviors","volume":"5","author":"M Pace","year":"2020","journal-title":"JCI insight"},{"issue":"9","key":"pone.0291995.ref042","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1038\/nm.3666","article-title":"The G protein \u03b1 subunit G\u03b1s is a tumor suppressor in Sonic hedgehog-driven medulloblastoma","volume":"20","author":"X He","year":"2014","journal-title":"Nat Med"},{"issue":"4","key":"pone.0291995.ref043","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.3390\/genes5041095","article-title":"Altered Actions of Memantine and NMDA-Induced Currents in a New Grid2-Deleted Mouse Line","volume":"5","author":"A Kumagai","year":"2014","journal-title":"Genes (Basel)"},{"issue":"24","key":"pone.0291995.ref044","doi-asserted-by":"crossref","first-page":"4947","DOI":"10.1242\/dev.097642","article-title":"Insm1 controls development of pituitary endocrine cells and requires a SNAG domain for function and for recruitment of histone-modifying factors","volume":"140","author":"JE Welcker","year":"2013","journal-title":"Development"},{"issue":"4","key":"pone.0291995.ref045","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.bbrc.2008.09.059","article-title":"Attenuated BDNF-induced upregulation of GABAergic markers in neurons lacking Xbp1","volume":"376","author":"A Hayashi","year":"2008","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"pone.0291995.ref046","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/j.nbd.2011.12.021","article-title":"Meta-analysis of genetic and environmental Parkinson\u2019s disease models reveals a common role of mitochondrial protection pathways","volume":"45","author":"L Soreq","year":"2012","journal-title":"Neurobiology of disease"},{"issue":"1","key":"pone.0291995.ref047","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto Encyclopedia of Genes and Genomes","volume":"28","author":"M Kanehisa","year":"2000","journal-title":"Nucleic Acids Research"},{"key":"pone.0291995.ref048","unstructured":"Oliveros JC. VENNY. An interactive tool for comparing lists with Venn Diagrams. https:\/\/bioinfogp.cnb.csic.es\/tools\/venny\/index.html. 2007."},{"issue":"3","key":"pone.0291995.ref049","doi-asserted-by":"crossref","first-page":"e1002270","DOI":"10.1371\/journal.pmed.1002270","article-title":"APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases","volume":"14","author":"H-M Lanoisel\u00e9e","year":"2017","journal-title":"PLoS medicine"},{"issue":"8","key":"pone.0291995.ref050","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.arcmed.2012.10.017","article-title":"Genetics of Alzheimer\u2019s disease","volume":"43","author":"MEA Vilatela","year":"2012","journal-title":"Archives of medical research"},{"issue":"1","key":"pone.0291995.ref051","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2006476118","article-title":"The Parkinson\u2019s disease-associated gene ITPKB protects against \u03b1-synuclein aggregation by regulating ER-to-mitochondria calcium release","volume":"118","author":"DJ Apicco","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0291995.ref052","first-page":"1043","article-title":"Microglia-Derived Extracellular Vesicles Carrying miR-711 Alleviate Neurodegeneration in a Murine Alzheimer\u2019s Disease Model by Binding to Itpkb","volume":"8","author":"Y Zhang","year":"2020","journal-title":"Frontiers in cell and developmental biology"},{"issue":"9","key":"pone.0291995.ref053","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.15252\/emmm.201606520","article-title":"miR-132 loss de-represses ITPKB and aggravates amyloid and TAU pathology in Alzheimer\u2019s brain","volume":"8","author":"E Salta","year":"2016","journal-title":"EMBO molecular medicine"},{"issue":"Pt 2","key":"pone.0291995.ref054","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1093\/brain\/awt344","article-title":"Inositol trisphosphate 3-kinase B is increased in human Alzheimer brain and exacerbates mouse Alzheimer pathology","volume":"137","author":"V Stygelbout","year":"2014","journal-title":"Brain"},{"issue":"7638","key":"pone.0291995.ref055","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"SA Liddelow","year":"2017","journal-title":"Nature"},{"issue":"17","key":"pone.0291995.ref056","doi-asserted-by":"crossref","first-page":"7439","DOI":"10.1523\/JNEUROSCI.4506-12.2013","article-title":"Phenotypic conversions of \u201cprotoplasmic\u201d to \u201creactive\u201d astrocytes in Alexander disease","volume":"33","author":"AA Sosunov","year":"2013","journal-title":"Journal of Neuroscience"},{"issue":"18","key":"pone.0291995.ref057","doi-asserted-by":"crossref","first-page":"6391","DOI":"10.1523\/JNEUROSCI.6221-11.2012","article-title":"Genomic analysis of reactive astrogliosis","volume":"32","author":"JL Zamanian","year":"2012","journal-title":"Journal of neuroscience"},{"key":"pone.0291995.ref058","first-page":"1","article-title":"Divergent transcriptional regulation of astrocyte reactivity across disorders","author":"JE Burda","year":"2022","journal-title":"Nature"},{"issue":"4","key":"pone.0291995.ref059","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1097\/00002093-199910000-00010","article-title":"Alexander disease: Alzheimer disease of the developing brain?","volume":"13","author":"R Castellani","year":"1999","journal-title":"Alzheimer disease and associated disorders"},{"issue":"7","key":"pone.0291995.ref060","article-title":"Astrocyte senescence as a component of Alzheimer\u2019s disease","author":"R Bhat","year":"2012","journal-title":"PLoS One"},{"issue":"12","key":"pone.0291995.ref061","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1523\/JNEUROSCI.1659-21.2021","article-title":"Anastasis drives senescence and non-cell autonomous neurodegeneration in the astrogliopathy Alexander disease","volume":"42","author":"L Wang","year":"2022","journal-title":"Journal of Neuroscience"},{"key":"pone.0291995.ref062","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3389\/fnagi.2016.00208","article-title":"Changes in the transcriptome of human astrocytes accompanying oxidative stress-induced senescence","volume":"8","author":"EP Crowe","year":"2016","journal-title":"Frontiers in aging neuroscience"},{"issue":"33","key":"pone.0291995.ref063","doi-asserted-by":"crossref","first-page":"29983","DOI":"10.1074\/jbc.M112121200","article-title":"A new splice variant of glial fibrillary acidic protein, GFAP\u03b5, interacts with the presenilin proteins","volume":"277","author":"AL Nielsen","year":"2002","journal-title":"Journal of Biological Chemistry"},{"issue":"9770","key":"pone.0291995.ref064","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/S0140-6736(10)61349-9","article-title":"Alzheimer\u2019s disease","volume":"377","author":"C Ballard","year":"2011","journal-title":"the Lancet"},{"issue":"3","key":"pone.0291995.ref065","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/ana.20406","article-title":"Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease","volume":"57","author":"R Li","year":"2005","journal-title":"Annals of neurology"},{"key":"pone.0291995.ref066","doi-asserted-by":"crossref","DOI":"10.1007\/3-540-27660-2","volume-title":"Magnetic resonance of myelination and myelin disorders","author":"MS Van der Knaap","year":"2005"},{"key":"pone.0291995.ref067","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1007\/s00415-011-6056-3","article-title":"Nationwide survey of Alexander disease in Japan and proposed new guidelines for diagnosis","volume":"258","author":"T Yoshida","year":"2011","journal-title":"Journal of neurology"},{"key":"pone.0291995.ref068","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jns.2019.04.030","article-title":"Neuropsychological features of adult form of Alexander disease","volume":"401","author":"L Draghi","year":"2019","journal-title":"Journal of the Neurological Sciences"},{"issue":"19","key":"pone.0291995.ref069","doi-asserted-by":"crossref","first-page":"6448","DOI":"10.1523\/JNEUROSCI.0248-14.2014","article-title":"Astrocytic TDP-43 pathology in Alexander disease","volume":"34","author":"AK Walker","year":"2014","journal-title":"Journal of Neuroscience"},{"key":"pone.0291995.ref070","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.brainres.2007.09.048","article-title":"Concurrence of TDP-43, tau and \u03b1-synuclein pathology in brains of Alzheimer\u2019s disease and dementia with Lewy bodies","volume":"1184","author":"S Higashi","year":"2007","journal-title":"Brain research"},{"issue":"7","key":"pone.0291995.ref071","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1093\/brain\/awy146","article-title":"Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated","volume":"141","author":"JL Robinson","year":"2018","journal-title":"Brain"},{"issue":"5","key":"pone.0291995.ref072","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.neurobiolaging.2006.11.014","article-title":"Olfaction in patients with mild cognitive impairment and Alzheimer\u2019s disease","volume":"29","author":"J Djordjevic","year":"2008","journal-title":"Neurobiology of Aging"},{"key":"pone.0291995.ref073","doi-asserted-by":"crossref","first-page":"101664","DOI":"10.1016\/j.nicl.2019.101664","article-title":"Increased brain age in adults with Prader-Willi syndrome","volume":"21","author":"AM Azor","year":"2019","journal-title":"NeuroImage: Clinical"},{"issue":"5","key":"pone.0291995.ref074","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.neuint.2004.03.007","article-title":"Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer\u2019s disease","volume":"45","author":"MR Hynd","year":"2004","journal-title":"Neurochemistry International"},{"issue":"6","key":"pone.0291995.ref075","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/cdd.2009.14","article-title":"Preventing oxidative stress: a new role for XBP1","volume":"16","author":"Y Liu","year":"2009","journal-title":"Cell Death & Differentiation"},{"issue":"2","key":"pone.0291995.ref076","doi-asserted-by":"crossref","first-page":"e89321","DOI":"10.1371\/journal.pone.0089321","article-title":"Gene expression alterations in the cerebellum and granule neurons of Cstb(-\/-) mouse are associated with early synaptic changes and inflammation","volume":"9","author":"T Joensuu","year":"2014","journal-title":"PLoS One"},{"key":"pone.0291995.ref077","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/s12016-013-8402-y","article-title":"TLR2 and TLR4 in autoimmune diseases: a comprehensive review","volume":"47","author":"Y Liu","year":"2014","journal-title":"Clinical reviews in allergy & immunology"},{"key":"pone.0291995.ref078","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.bjid.2015.10.011","article-title":"TLR2 and TLR4 mediated host immune responses in major infectious diseases: a review","volume":"20","author":"S Mukherjee","year":"2016","journal-title":"Brazilian Journal of Infectious Diseases"},{"key":"pone.0291995.ref079","doi-asserted-by":"crossref","first-page":"602508","DOI":"10.3389\/fnins.2020.602508","article-title":"TLR4 targeting as a promising therapeutic strategy for Alzheimer disease treatment","volume":"14","author":"Y Zhou","year":"2020","journal-title":"Frontiers in Neuroscience"},{"issue":"2","key":"pone.0291995.ref080","doi-asserted-by":"crossref","first-page":"383","DOI":"10.3390\/cells9020383","article-title":"Impact of HMGB1, RAGE, and TLR4 in Alzheimer\u2019s disease (AD): from risk factors to therapeutic targeting","volume":"9","author":"YN Paudel","year":"2020","journal-title":"Cells"},{"issue":"3","key":"pone.0291995.ref081","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.4049\/jimmunol.1101121","article-title":"TLR2 is a primary receptor for Alzheimer\u2019s amyloid \u03b2 peptide to trigger neuroinflammatory activation","volume":"188","author":"S Liu","year":"2012","journal-title":"The Journal of Immunology"},{"issue":"8","key":"pone.0291995.ref082","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.4103\/1673-5374.303016","article-title":"TLR2 and TLR4-mediated inflammation in Alzheimer\u2019s disease: self-defense or sabotage?","volume":"16","author":"ML Dallas","year":"2021","journal-title":"Neural Regeneration Research"},{"issue":"40","key":"pone.0291995.ref083","doi-asserted-by":"crossref","first-page":"10129","DOI":"10.1523\/JNEUROSCI.1202-06.2006","article-title":"Intraneuronal \u03b2-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer\u2019s disease mutations: potential factors in amyloid plaque formation","volume":"26","author":"H Oakley","year":"2006","journal-title":"Journal of Neuroscience"},{"issue":"1","key":"pone.0291995.ref084","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13024-017-0231-7","article-title":"Practical considerations for choosing a mouse model of Alzheimer\u2019s disease","volume":"12","author":"JL Jankowsky","year":"2017","journal-title":"Molecular Neurodegeneration"},{"issue":"17","key":"pone.0291995.ref085","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.15252\/embj.201797397","article-title":"APP mouse models for Alzheimer\u2019s disease preclinical studies","volume":"36","author":"H Sasaguri","year":"2017","journal-title":"The EMBO journal"},{"issue":"6","key":"pone.0291995.ref086","doi-asserted-by":"crossref","first-page":"628","DOI":"10.2174\/156720512801322573","article-title":"Overview and findings from the religious orders study","volume":"9","author":"DA Bennett","year":"2012","journal-title":"Current Alzheimer Research"},{"key":"pone.0291995.ref087","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.3389\/fimmu.2019.01170","article-title":"The transcriptional landscape of microglial genes in aging and neurodegenerative disease","volume":"10","author":"LW Bonham","year":"2019","journal-title":"Frontiers in immunology"},{"issue":"1","key":"pone.0291995.ref088","doi-asserted-by":"crossref","first-page":"180142","DOI":"10.1038\/sdata.2018.142","article-title":"A multi-omic atlas of the human frontal cortex for aging and Alzheimer\u2019s disease research","volume":"5","author":"PL De Jager","year":"2018","journal-title":"Scientific Data"},{"key":"pone.0291995.ref089","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1007\/s00401-017-1737-3","article-title":"Deficiency of TYROBP, an adapter protein for TREM2 and CR3 receptors, is neuroprotective in a mouse model of early Alzheimer\u2019s pathology","volume":"134","author":"J-V Haure-Mirande","year":"2017","journal-title":"Acta neuropathologica"},{"issue":"W1","key":"pone.0291995.ref090","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"MV Kuleshov","year":"2016","journal-title":"Nucleic Acids Research"},{"issue":"1","key":"pone.0291995.ref091","doi-asserted-by":"crossref","first-page":"7580","DOI":"10.1038\/s41598-019-43935-8","article-title":"GREIN: An Interactive Web Platform for Re-analyzing GEO RNA-seq Data","volume":"9","author":"NA Mahi","year":"2019","journal-title":"Scientific Reports"},{"issue":"D1","key":"pone.0291995.ref092","doi-asserted-by":"crossref","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: archive for functional genomics data sets\u2014update","volume":"41","author":"T Barrett","year":"2012","journal-title":"Nucleic Acids Research"},{"key":"pone.0291995.ref093","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1007\/s00439-001-0615-0","article-title":"The HUGO gene nomenclature committee (HGNC)","volume":"109","author":"S Povey","year":"2001","journal-title":"Human genetics"},{"key":"pone.0291995.ref094","unstructured":"Council NR. Guide for the care and use of laboratory animals. 2010."},{"issue":"1","key":"pone.0291995.ref095","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2105-15-182","article-title":"Skewer: a fast and accurate adapter trimmer for next-generation sequencing paired-end reads","volume":"15","author":"H Jiang","year":"2014","journal-title":"BMC bioinformatics"},{"issue":"1","key":"pone.0291995.ref096","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"A Dobin","year":"2013","journal-title":"Bioinformatics"},{"issue":"1","key":"pone.0291995.ref097","first-page":"1","article-title":"RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome","volume":"12","author":"B Li","year":"2011","journal-title":"BMC bioinformatics"},{"issue":"1","key":"pone.0291995.ref098","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"MD Robinson","year":"2009","journal-title":"Bioinformatics"},{"issue":"6","key":"pone.0291995.ref099","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1038\/nprot.2014.085","article-title":"Cell type\u2013specific mRNA purification by translating ribosome affinity purification (TRAP)","volume":"9","author":"M Heiman","year":"2014","journal-title":"Nature protocols"},{"issue":"4","key":"pone.0291995.ref100","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.cell.2008.10.029","article-title":"Application of a translational profiling approach for the comparative analysis of CNS cell types","volume":"135","author":"JP Doyle","year":"2008","journal-title":"Cell"},{"issue":"3","key":"pone.0291995.ref101","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/gb-2009-10-3-r25","article-title":"Ultrafast and memory-efficient alignment of short DNA sequences to the human genome","volume":"10","author":"B Langmead","year":"2009","journal-title":"Genome biology"},{"key":"pone.0291995.ref102","unstructured":"Prada C, Lima D, Helder N. MetaVolcanoR: Gene Expression Meta-analysis Visualization Tool. R package version 1.4.0. ed. Bioconductor2020."},{"issue":"1","key":"pone.0291995.ref103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/sdata.2016.89","article-title":"Human whole genome genotype and transcriptome data for Alzheimer\u2019s and other neurodegenerative diseases","volume":"3","author":"M Allen","year":"2016","journal-title":"Scientific data"},{"issue":"1","key":"pone.0291995.ref104","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/sdata.2018.185","article-title":"The Mount Sinai cohort of large-scale genomic, transcriptomic and proteomic data in Alzheimer\u2019s disease","volume":"5","author":"M Wang","year":"2018","journal-title":"Scientific data"},{"key":"pone.0291995.ref105","unstructured":"Team RC. R: A language and environment for statistical computing. 2013."},{"issue":"1","key":"pone.0291995.ref106","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-021-83348-0","article-title":"Creation of a gene expression portrait of depression and its application for identifying potential treatments","volume":"11","author":"SC Gammie","year":"2021","journal-title":"Scientific reports"},{"issue":"3","key":"pone.0291995.ref107","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1109\/MCSE.2007.58","article-title":"Python for scientific computing","volume":"9","author":"TE Oliphant","year":"2007","journal-title":"Computing in science & engineering"},{"issue":"5","key":"pone.0291995.ref108","first-page":"S5","article-title":"Introduction to Anaconda and Python: Installation and setup","volume":"16","author":"D Rolon-M\u00e9rette","year":"2016","journal-title":"Python for research in psychology"},{"issue":"suppl_2","key":"pone.0291995.ref109","doi-asserted-by":"crossref","first-page":"W96","DOI":"10.1093\/nar\/gkq418","article-title":"ToppCluster: a multiple gene list feature analyzer for comparative enrichment clustering and network-based dissection of biological systems","volume":"38","author":"V Kaimal","year":"2010","journal-title":"Nucleic Acids Research"},{"key":"pone.0291995.ref110","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/978-3-642-18638-7_8","volume-title":"Graph Drawing Software","author":"R Wiese","year":"2004"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0291995","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T18:30:06Z","timestamp":1705602606000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0291995"}},"subtitle":[],"editor":[{"given":"Firas H","family":"Kobeissy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,1,18]]},"references-count":110,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0291995","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,18]]}}}