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However, there is a gap in regard to analyzing different forms of early-onset dementia and the use of Lymphoblastoid cell lines (LCLs). We performed a genome-wide DNA methylation analysis on sixty-four samples (from the prefrontal cortex and LCLs) including those taken from patients with early-onset forms of Alzheimer\u2019s disease (AD) and frontotemporal dementia (FTD) and healthy controls. A beta regression model and adjusted p-values were used to obtain differentially methylated positions (DMPs) via pairwise comparisons. A correlation analysis of DMP levels with Clariom D array gene expression data from the same cohort was also performed. The results showed hypermethylation as the most frequent finding in both tissues studied in the patient groups. Biological significance analysis revealed common pathways altered in AD and FTD patients, affecting neuron development, metabolism, signal transduction, and immune system pathways. These alterations were also found in LCL samples, suggesting the epigenetic changes might not be limited to the central nervous system. In the brain, CpG methylation presented an inverse correlation with gene expression, while in LCLs, we observed mainly a positive correlation. This study enhances our understanding of the biological pathways that are associated with neurodegeneration, describes differential methylation patterns, and suggests LCLs are a potential cell model for studying neurodegenerative diseases in earlier clinical phases than brain tissue.<\/jats:p>","DOI":"10.3390\/ijms25105445","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T11:26:17Z","timestamp":1715858777000},"page":"5445","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genome-Wide DNA Methylation in Early-Onset-Dementia Patients Brain Tissue and Lymphoblastoid Cell Lines"],"prefix":"10.3390","volume":"25","author":[{"given":"Oscar","family":"Ramos-Campoy","sequence":"first","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Cl\u00ednic de Barcelona, FRCB-IDIBAPS, Universitat de Barcelona (UB), 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aina","family":"Comas-Albert\u00ed","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Cl\u00ednic de Barcelona, FRCB-IDIBAPS, Universitat de Barcelona (UB), 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0635-4961","authenticated-orcid":false,"given":"David","family":"Herv\u00e1s","sequence":"additional","affiliation":[{"name":"Department of Applied Statistics and Operations Research and Quality, Universitat Polit\u00e8cnica de Val\u00e8ncia, 46022 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2557-0010","authenticated-orcid":false,"given":"Sergi","family":"Borrego-\u00c9cija","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Neurology 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Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5200-3164","authenticated-orcid":false,"given":"Ferm\u00edn","family":"Moreno-Izco","sequence":"additional","affiliation":[{"name":"Cognitive Disorders Unit, Department of Neurology, Hospital Universitario Donostia, 20014 San Sebastian, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Biogipuzkoa, Neurosciences Area, Group of Neurodegenerative Diseases, 20014 San Sebastian, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guadalupe","family":"Fern\u00e1ndez-Villullas","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Cl\u00ednic de Barcelona, FRCB-IDIBAPS, Universitat de Barcelona (UB), 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4068-8578","authenticated-orcid":false,"given":"Laura","family":"Molina-Porcel","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Cl\u00ednic de Barcelona, FRCB-IDIBAPS, Universitat de Barcelona (UB), 08036 Barcelona, Spain"},{"name":"Neurological Tissue Bank, Biobank-Hospital Clinic-IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mircea","family":"Balasa","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Cl\u00ednic de Barcelona, FRCB-IDIBAPS, Universitat de Barcelona (UB), 08036 Barcelona, 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Early-Onset Alzheimer\u2019s Disease and Frontotemporal Dementia Neuroimaging Signatures","volume":"41","author":"Antonell","year":"2020","journal-title":"Hum. Brain Mapp."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"fcab308","DOI":"10.1093\/braincomms\/fcab308","article-title":"Measuring Heritable Contributions to Alzheimer\u2019s Disease: Polygenic Risk Score Analysis with Twins","volume":"4","author":"Karlsson","year":"2022","journal-title":"Brain Commun."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Rujeedawa, T., Carrillo, E., Clare, I.C.H., Fortea, J., Strydom, A., Rebillat, A., Coppus, A., Levin, J., and Zaman, S.H. (2021). The Clinical and Neuropathological Features of Sporadic (Late-Onset) and Genetic Forms of Alzheimer\u2019s Disease. J. Clin. Med., 10.","DOI":"10.3390\/jcm10194582"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/S1474-4422(21)00341-0","article-title":"Advances and Controversies in Frontotemporal Dementia: Diagnosis, Biomarkers, and Therapeutic Considerations","volume":"21","author":"Boeve","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.psc.2020.02.006","article-title":"Frontotemporal Dementia: Neuropathology, Genetics, Neuroimaging, and Treatments","volume":"43","author":"Younes","year":"2020","journal-title":"Psychiatr. Clin. N. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/npp.2012.112","article-title":"DNA Methylation and Its Basic Function","volume":"38","author":"Moore","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1038\/nn.3782","article-title":"Cross-Tissue Methylomic Profiling Strongly Implicates a Role for Cortex-Specific Deregulation of ANK1 in Alzheimer\u2019s Disease Neuropathology","volume":"17","author":"Lunnon","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"977","DOI":"10.3233\/JAD-141989","article-title":"Integrated Whole Transcriptome and DNA Methylation Analysis Identifies Gene Networks Specific to Late-Onset Alzheimer\u2019s Disease","volume":"44","author":"Humphries","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1007\/s12035-016-0357-6","article-title":"Epigenetics in Alzheimer\u2019s Disease: Perspective of DNA Methylation","volume":"55","author":"Qazi","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zimmer-Bensch, G., and Zempel, H. (2021). DNA Methylation in Genetic and Sporadic Forms of Neurodegeneration: Lessons from Alzheimer\u2019s, Related Tauopathies and Genetic Tauopathies. Cells, 10.","DOI":"10.20944\/preprints202105.0717.v1"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111319","DOI":"10.1016\/j.mad.2020.111319","article-title":"DNA Methylation in Alzheimer\u2019s Disease: In Brain and Peripheral Blood","volume":"191","author":"Wei","year":"2020","journal-title":"Mech. Ageing Dev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4852","DOI":"10.1038\/s41467-022-32475-x","article-title":"Cross-Tissue Analysis of Blood and Brain Epigenome-Wide Association Studies in Alzheimer\u2019s Disease","volume":"13","author":"Silva","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s00401-016-1587-4","article-title":"ALS and FTD: An Epigenetic Perspective","volume":"132","author":"Belzil","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/2051-5960-1-16","article-title":"Promoter DNA Methylation Regulates Progranulin Expression and Is Altered in FTLD","volume":"1","author":"Claus","year":"2013","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13024-020-0359-8","article-title":"Elevated Methylation Levels, Reduced Expression Levels, and Frequent Contractions in a Clinical Cohort of C9orf72 Expansion Carriers","volume":"15","author":"Jackson","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"633668","DOI":"10.3389\/fncel.2021.633668","article-title":"Hypothesis and Theory: Roles of Arginine Methylation in C9orf72-Mediated ALS and FTD","volume":"15","author":"Gill","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1038\/s41593-023-01374-9","article-title":"Globally Reduced N 6-Methyladenosine (M6A) in C9ORF72-ALS\/FTD Dysregulates RNA Metabolism and Contributes to Neurodegeneration","volume":"26","author":"Li","year":"2023","journal-title":"Nat. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1080\/21678421.2021.1962355","article-title":"Genetic and Epigenetic Disease Modifiers in an Italian C9orf72 Family Expressing ALS, FTD or PD Clinical Phenotypes","volume":"23","author":"Ratti","year":"2022","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.jns.2016.02.004","article-title":"Gene Promoter Methylation and Expression of Pin1 Differ between Patients with Frontotemporal Dementia and Alzheimer\u2019s Disease","volume":"362","author":"Ferri","year":"2016","journal-title":"J. Neurol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Iglesias, O., Naidoo, V., Cacabelos, N., and Cacabelos, R. (2022). Epigenetic Biomarkers as Diagnostic Tools for Neurodegenerative Disorders. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010013"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e718","DOI":"10.1038\/tp.2015.214","article-title":"Human DNA Methylomes of Neurodegenerative Diseases Show Common Epigenomic Patterns","volume":"6","author":"Heyn","year":"2016","journal-title":"Transl. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Nabais, M.F., Laws, S.M., Lin, T., Vallerga, C.L., Armstrong, N.J., Blair, I.P., Kwok, J.B., Mather, K.A., Mellick, G.D., and Sachdev, P.S. (2021). Meta-Analysis of Genome-Wide DNA Methylation Identifies Shared Associations across Neurodegenerative Disorders. Genome Biol., 22.","DOI":"10.1186\/s13059-021-02275-5"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"737","DOI":"10.3233\/JAD-160278","article-title":"Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate between Down Syndrome and Alzheimer\u2019s Disease","volume":"55","author":"Coskun","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lastres-Becker, I., Porras, G., Arribas-Bl\u00e1zquez, M., Maestro, I., Borrego-Hern\u00e1ndez, D., Boya, P., Cerd\u00e1n, S., Garc\u00eda-Redondo, A., Mart\u00ednez, A., and Martin-Requero, \u00c1. (2021). Molecular Alterations in Sporadic and SOD1-ALS Immortalized Lymphocytes: Towards a Personalized Therapy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063007"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Cuevas, E.P., Martinez-Gonzalez, L., Gordillo, C., Tosat-Bitri\u00e1n, C., P\u00e9rez de la Lastra, C., S\u00e1enz, A., Gil, C., Palomo, V., Martin-Requero, \u00c1., and Martinez, A. (2024). Casein Kinase 1 Inhibitor Avoids TDP-43 Pathology Propagation in a Patient-Derived Cellular Model of Amyotrophic Lateral Sclerosis. Neurobiol. Dis., 192.","DOI":"10.1016\/j.nbd.2024.106430"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Peri\u00f1\u00e1n, G., de la Encarnaci\u00f3n, A., Moreno, F., L\u00f3pez de Munain, A., Mart\u00ednez, A., Mart\u00edn-Requero, \u00c1., Alqu\u00e9zar, C., and Bartolom\u00e9, F. (2023). Progranulin Deficiency Induces Mitochondrial Dysfunction in Frontotemporal Lobar Degeneration with TDP-43 Inclusions. Antioxidants, 12.","DOI":"10.3390\/antiox12030581"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.bbi.2014.11.002","article-title":"Global Changes in DNA Methylation in Alzheimer\u2019s Disease Peripheral Blood Mononuclear Cells","volume":"45","author":"Arosio","year":"2015","journal-title":"Brain. Behav. Immun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s00401-014-1286-y","article-title":"C9orf72 Hypermethylation Protects against Repeat Expansion-Associated Pathology in ALS\/FTD","volume":"128","author":"Liu","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6411","DOI":"10.1007\/s12035-022-02969-2","article-title":"Differential Gene Expression in Sporadic and Genetic Forms of Alzheimer\u2019 s Disease and Frontotemporal Dementia in Brain Tissue and Lymphoblastoid Cell Lines","volume":"59","author":"Bosch","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s00401-019-01966-5","article-title":"Integrated DNA Methylation and Gene Expression Profiling across Multiple Brain Regions Implicate Novel Genes in Alzheimer\u2019s Disease","volume":"137","author":"Semick","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.2217\/epi-2017-0160","article-title":"Alzheimer\u2019s Disease DNA Methylome of Pyramidal Layers in Frontal Cortex: Laser-Assisted Microdissection Study","volume":"10","author":"Zelaya","year":"2018","journal-title":"Epigenomics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"571","DOI":"10.3233\/JAD-2012-111223","article-title":"Genome-Wide DNA Methylation Differences between Late-Onset Alzheimer\u2019s Disease and Cognitively Normal Controls in Human Frontal Cortex","volume":"29","author":"Bakulski","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s13148-019-0672-7","article-title":"DNA Methylation Signature of Human Hippocampus in Alzheimer\u2019s Disease Is Linked to Neurogenesis","volume":"11","author":"Altuna","year":"2019","journal-title":"Clin. Epigenetics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1038\/s41467-019-10101-7","article-title":"Epigenetic Dysregulation of Enhancers in Neurons Is Associated with Alzheimer\u2019s Disease Pathology and Cognitive Symptoms","volume":"10","author":"Li","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13072-018-0211-3","article-title":"DNA Methylation Analysis on Purified Neurons and Glia Dissects Age and Alzheimer\u2019s Disease-Specific Changes in the Human Cortex","volume":"11","author":"Gasparoni","year":"2018","journal-title":"Epigenetics Chromatin"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.18632\/aging.100864","article-title":"Epigenetic Age of the Pre-Frontal Cortex Is Associated with Neuritic Plaques, Amyloid Load, and Alzheimer\u2019s Disease Related Cognitive Functioning","volume":"7","author":"Levine","year":"2015","journal-title":"Aging (Albany NY)"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s13148-019-0755-5","article-title":"Alzheimer\u2019s Disease-Associated (Hydroxy)Methylomic Changes in the Brain and Blood","volume":"11","author":"Lardenoije","year":"2019","journal-title":"Clin. Epigenetics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.jalz.2016.02.009","article-title":"Methylation Profiles in Peripheral Blood CD4+ Lymphocytes versus Brain: The Relation to Alzheimer\u2019s Disease Pathology","volume":"12","author":"Yu","year":"2016","journal-title":"Alzheimers Dement."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"19089","DOI":"10.18632\/oncotarget.7862","article-title":"Common DNA Methylation Alterations of Alzheimer\u2019s Disease and Aging in Peripheral Whole Blood","volume":"7","author":"Li","year":"2016","journal-title":"Oncotarget"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8899","DOI":"10.1038\/s41598-017-09320-z","article-title":"Susceptible Genes and Disease Mechanisms Identified in Frontotemporal Dementia and Frontotemporal Dementia with Amyotrophic Lateral Sclerosis by DNA-Methylation and GWAS","volume":"7","author":"Taskesen","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Li, Y., Chen, J.A., Sears, R.L., Gao, F., Klein, E.D., Karydas, A., Geschwind, M.D., Rosen, H.J., Boxer, A.L., and Guo, W. (2014). An Epigenetic Signature in Peripheral Blood Associated with the Haplotype on 17q21.31, a Risk Factor for Neurodegenerative Tauopathy. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004211"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3389\/fnagi.2020.00016","article-title":"Genetic Association of FERMT2, HLA-DRB1, CD2AP, and PTK2B Polymorphisms With Alzheimer\u2019s Disease Risk in the Southern Chinese Population","volume":"12","author":"Yan","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"153331752210850","DOI":"10.1177\/15333175221085066","article-title":"Regulation of the Late Onset Alzheimer\u2019s Disease Associated HLA-DQA1\/DRB1 Expression","volume":"37","author":"Zhang","year":"2022","journal-title":"Am. J. Alzheimers Dis. Other Dement."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/nan.12023","article-title":"The Cell Survival Kinase SGK1 and Its Targets FOXO3a and NDRG1 in Aged Human Brain","volume":"39","author":"Sahin","year":"2013","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1001\/jamaneurol.2014.4040","article-title":"A Multiancestral Genome-Wide Exome Array Study of Alzheimer Disease, Frontotemporal Dementia, and Progressive Supranuclear Palsy","volume":"72","author":"Chen","year":"2015","journal-title":"JAMA Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1007\/s00401-017-1685-y","article-title":"Genome-Wide Association Study Identifies Four Novel Loci Associated with Alzheimer\u2019s Endophenotypes and Disease Modifiers","volume":"133","author":"Deming","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13024-022-00536-w","article-title":"Van The Role of ATP-Binding Cassette Subfamily A in the Etiology of Alzheimer\u2019 s Disease","volume":"17","author":"Bossaerts","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.neurobiolaging.2018.09.008","article-title":"Common and Rare GCH1 Variants Are Associated with Parkinson\u2019s Disease","volume":"73","author":"Rudakou","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"8065","DOI":"10.1074\/jbc.RA117.000490","article-title":"Annexins A2 and A6 Interact with the Extreme N Terminus of Tau and Thereby Contribute to Tau\u2019s Axonal Localization","volume":"293","author":"Alonso","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Noori, A., Mezlini, A.M., Hyman, B.T., Serrano-Pozo, A., and Das, S. (2021). Systematic Review and Meta-Analysis of Human Transcriptomics Reveals Neuroinflammation, Deficient Energy Metabolism, and Proteostasis Failure across Neurodegeneration. Neurobiol. Dis., 149.","DOI":"10.1016\/j.nbd.2020.105225"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13073-015-0258-8","article-title":"Genome-Wide DNA Methylation Profiling in the Superior Temporal Gyrus Reveals Epigenetic Signatures Associated with Alzheimer\u2019s Disease","volume":"8","author":"Watson","year":"2016","journal-title":"Genome Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.neurobiolaging.2020.09.019","article-title":"Mendelian Randomization Integrating GWAS and MQTL Data Identified Novel Pleiotropic DNA Methylation Loci for Neuropathology of Alzheimer\u2019s Disease","volume":"97","author":"Liu","year":"2021","journal-title":"Neurobiol. Aging"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.neurobiolaging.2018.12.003","article-title":"DNA Methylation Variability in Alzheimer\u2019s Disease","volume":"76","author":"Huo","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13072-017-0150-4","article-title":"Neuroepigenetic Mechanisms in Disease","volume":"10","author":"Christopher","year":"2017","journal-title":"Epigenetics Chromatin"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3389\/fnmol.2017.00069","article-title":"Whole Genome Expression Analysis in a Mouse Model of Tauopathy Identifies MECP2 as a Possible Regulator of Tau Pathology","volume":"10","author":"Maphis","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.7150\/thno.68439","article-title":"Dysfunction of Striatal MeCP2 Is Associated with Cognitive Decline in a Mouse Model of Alzheimer\u2019s Disease","volume":"12","author":"Lee","year":"2022","journal-title":"Theranostics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"620859","DOI":"10.3389\/fgene.2021.620859","article-title":"MeCP2: The Genetic Driver of Rett Syndrome Epigenetics","volume":"12","author":"Good","year":"2021","journal-title":"Front. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"616614","DOI":"10.3389\/fnagi.2020.616614","article-title":"AD7c-NTP Impairs Adult Striatal Neurogenesis by Affecting the Biological Function of MeCP2 in APP\/PSl Transgenic Mouse Model of Alzheimer\u2019s Disease","volume":"12","author":"Li","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1007\/s00018-023-04845-1","article-title":"Epigenetic Silencing of OR and TAS2R Genes Expression in Human Orbitofrontal Cortex at Early Stages of Sporadic Alzheimer\u2019s Disease","volume":"80","author":"Alves","year":"2023","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.redox.2013.07.003","article-title":"Cullin 3 as a Novel Target in Diverse Pathologies","volume":"1","year":"2013","journal-title":"Redox Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s12539-019-00353-8","article-title":"Identification of Key Regulatory Genes and Pathways in Prefrontal Cortex of Alzheimer\u2019s Disease","volume":"12","author":"Yang","year":"2020","journal-title":"Interdiscip. Sci. Comput. Life Sci."},{"key":"ref_63","first-page":"1791","article-title":"DNAJB6b Is Downregulated in Synucleinopathies","volume":"11","author":"Folke","year":"2021","journal-title":"J. Park. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.clineuro.2014.09.013","article-title":"Pathology of Frontotemporal Dementia with Limb Girdle Muscular Dystrophy Caused by a DNAJB6 Mutation","volume":"127","author":"Yabe","year":"2014","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.neurobiolaging.2015.02.017","article-title":"Stratified Gene Expression Analysis Identifies Major Amyotrophic Lateral Sclerosis Genes","volume":"36","author":"Jones","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1093\/brain\/awy238","article-title":"A C6orf10\/LOC101929163 Locus Is Associated with Age of Onset in C9orf72 Carriers","volume":"141","author":"Zhang","year":"2018","journal-title":"Brain"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1002\/acn3.745","article-title":"Novel CSF Biomarkers in Genetic Frontotemporal Dementia Identified by Proteomics","volume":"6","author":"Meeter","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1111\/ene.15248","article-title":"Rare Variants in TP73 in a Frontotemporal Dementia Cohort Link This Gene with Primary Progressive Aphasia Phenotypes","volume":"29","author":"Santana","year":"2022","journal-title":"Eur. J. Neurol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1114022","DOI":"10.3389\/fnagi.2023.1114022","article-title":"Genetic and Clinical Analysis of TP73 Gene in Amyotrophic Lateral Sclerosis Patients from Chinese Mainland","volume":"15","author":"Tang","year":"2023","journal-title":"Front. Aging Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/S1474-4422(14)70065-1","article-title":"Frontotemporal Dementia and Its Subtypes: A Genome-Wide Association Study","volume":"13","author":"Ferrari","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.gene.2019.02.026","article-title":"Construction of Parkinson\u2019s Disease Marker-Based Weighted Protein-Protein Interaction Network for Prioritization of Co-Expressed Genes","volume":"697","author":"George","year":"2019","journal-title":"Gene"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"535","DOI":"10.3233\/JAD-191230","article-title":"ErbB4 Mutation That Decreased NRG1-ErbB4 Signaling Involved in the Pathogenesis of Amyotrophic Lateral Sclerosis\/Frontotemporal Dementia","volume":"74","author":"Sun","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Wang, L., Shui, X., Diao, Y., Chen, D., Zhou, Y., and Lee, T.H. (2023). Potential Implications of MiRNAs in the Pathogenesis, Diagnosis, and Therapeutics of Alzheimer\u2019s Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216259"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Xu, J., and Liu, Y. (2021). Probing Chromatin Compaction and Its Epigenetic States in Situ With Single-Molecule Localization-Based Super-Resolution Microscopy. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.653077"},{"key":"ref_75","first-page":"3963","article-title":"Regulation of Histone Arginine Methylation\/Demethylation by Methylase and Demethylase (Review)","volume":"49","author":"Zhang","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1467-9868.2005.00503.x","article-title":"Regularization and Variable Selection via the Elastic Net","volume":"67","author":"Zou","year":"2005","journal-title":"J. R. Stat. Soc. Ser. B Stat. Methodol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Heberle, H., Meirelles, V.G., da Silva, F.R., Telles, G.P., and Minghim, R. (2015). InteractiVenn: A Web-Based Tool for the Analysis of Sets through Venn Diagrams. BMC Bioinform., 16.","DOI":"10.1186\/s12859-015-0611-3"},{"key":"ref_78","first-page":"D498","article-title":"The Reactome Pathway Knowledgebase","volume":"48","author":"Jassal","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"bap010","DOI":"10.1093\/database\/bap010","article-title":"QuickGO: A User Tutorial for the Web-Based Gene Ontology Browser","volume":"2009","author":"Huntley","year":"2009","journal-title":"Database"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5445\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:43:41Z","timestamp":1760107421000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5445"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,16]]},"references-count":79,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ijms25105445"],"URL":"https:\/\/doi.org\/10.3390\/ijms25105445","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,16]]}}}