{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:13:43Z","timestamp":1791278023869,"version":"4.1.0"},"reference-count":157,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T00:00:00Z","timestamp":1636243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["ZI1224\/13-1"],"award-info":[{"award-number":["ZI1224\/13-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["368482240\/GRK2416DFG"],"award-info":[{"award-number":["368482240\/GRK2416DFG"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Else-Kr\u00f6ner-Fresenius Stiftung","award":["2019_A41"],"award-info":[{"award-number":["2019_A41"]}]},{"name":"Koeln Fortune Program \/ Faculty of Medicine, University of Cologne","award":["475\/2020"],"award-info":[{"award-number":["475\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Genetic and sporadic forms of tauopathies, the most prevalent of which is Alzheimer\u2019s Disease, are a scourge of the aging society, and in the case of genetic forms, can also affect children and young adults. All tauopathies share ectopic expression, mislocalization, or aggregation of the microtubule associated protein TAU, encoded by the MAPT gene. As TAU is a neuronal protein widely expressed in the CNS, the overwhelming majority of tauopathies are neurological disorders. They are characterized by cognitive dysfunction often leading to dementia, and are frequently accompanied by movement abnormalities such as parkinsonism. Tauopathies can lead to severe neurological deficits and premature death. For some tauopathies there is a clear genetic cause and\/or an epigenetic contribution. However, for several others the disease etiology is unclear, with few tauopathies being environmentally triggered. Here, we review current knowledge of tauopathies listing known genetic and important sporadic forms of these disease. Further, we discuss how DNA methylation as a major epigenetic mechanism emerges to be involved in the disease pathophysiology of Alzheimer\u2019s, and related genetic and non-genetic tauopathies. Finally, we debate the application of epigenetic signatures in peripheral blood samples as diagnostic tools and usages of epigenetic therapy strategies for these diseases.<\/jats:p>","DOI":"10.3390\/cells10113064","type":"journal-article","created":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T20:41:14Z","timestamp":1636317674000},"page":"3064","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["DNA Methylation in Genetic and Sporadic Forms of Neurodegeneration: Lessons from Alzheimer\u2019s, Related Tauopathies and Genetic Tauopathies"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8894-8079","authenticated-orcid":false,"given":"Geraldine","family":"Zimmer-Bensch","sequence":"first","affiliation":[{"name":"Functional Epigenetics in the Animal Model, Institute for Biology II, RWTH Aachen University, 52074 Aachen, Germany"},{"name":"Research Training Group 2416 MultiSenses-MultiScales, Institute for Biology II, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7510-3077","authenticated-orcid":false,"given":"Hans","family":"Zempel","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.tins.2014.08.004","article-title":"Lost after translation: Missorting of Tau protein and consequences for Alzheimer disease","volume":"37","author":"Zempel","year":"2014","journal-title":"Trends Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/978-981-32-9358-8_6","article-title":"Mechanisms of Axonal Sorting of Tau and Influence of the Axon Initial Segment on Tau Cell Polarity","volume":"Volume 1184","author":"Zempel","year":"2019","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_3","first-page":"193","article-title":"Tau gene mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17)","volume":"2","author":"Spillantini","year":"2000","journal-title":"Neurogenetics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1097\/00002093-200210000-00001","article-title":"Relative Frequencies of Alzheimer Disease, Lewy Body, Vascular and Frontotemporal Dementia, and Hippocampal Sclerosis in the State of Florida Brain Bank","volume":"16","author":"Barker","year":"2016","journal-title":"Alzheimer Dis. 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