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We show that alterations in REST expression and sub-cellular localization are partially responsible for AD pathology, as REST overexpression improves cognition, reduces amyloid-\u03b2 and phosphorylated Tau deposition, and restores mitochondrial and synaptic homeostasis. Mechanistically, the NAD+\/SIRT1 axis modulates REST expression through chromatin remodelling in the promoter region of REST, leading to changes in the expression of REST target genes involved in mitophagy and synaptic function.<\/jats:p>\n                  <jats:p>These findings reveal a new mechanism of action for NAD+ and highlight REST as a promising therapeutic target for AD therapy.<\/jats:p>","DOI":"10.1093\/brain\/awaf261","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T11:54:00Z","timestamp":1753271640000},"page":"1208-1223","source":"Crossref","is-referenced-by-count":5,"title":["Loss of REST associated with Alzheimer's disease pathology is ameliorated by NAD+"],"prefix":"10.1093","volume":"149","author":[{"given":"Maria J","family":"Lagartos-Donate","sequence":"first","affiliation":[{"name":"Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital , L\u00f8renskog 1478 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Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biomedicine Institute, University of Castilla-La Mancha , Albacete 02071 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Anisimov","sequence":"additional","affiliation":[{"name":"Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital , L\u00f8renskog 1478 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola P","family":"Montaldo","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Oslo University Hospital , Oslo 0424 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidar","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Oslo , Oslo 0372 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Alzheimer\u2019s and Parkinson\u2019s diseases: The prion concept in relation to assembled A\u03b2, tau, and \u03b1-synuclein","volume":"349","author":"Goedert","year":"2015","journal-title":"Science"},{"key":"2026040804054688500_awaf261-B9","doi-asserted-by":"crossref","first-page":"101307","DOI":"10.1016\/j.arr.2021.101307","article-title":"Re-emphasizing early Alzheimer\u2019s disease pathology starting in select entorhinal neurons, with a special focus on mitophagy","volume":"67","author":"Kobro-Flatmoen","year":"2021","journal-title":"Ageing Res Rev"},{"key":"2026040804054688500_awaf261-B10","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.7150\/ijbs.57078","article-title":"Interaction between A\u03b2 and tau in the pathogenesis of Alzheimer's disease","volume":"17","author":"Zhang","year":"2021","journal-title":"Int J Biol 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