{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:09:41Z","timestamp":1779340181223,"version":"3.51.4"},"reference-count":89,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dimethyl fumarate (DMF), a fumaric acid ester, is approved for psoriasis and multiple sclerosis due to its antioxidant and anti-inflammatory properties mediated via Nrf2 activation. Nrf2 regulates genes that protect cells from oxidative stress, a key factor in neurodegenerative diseases such as Alzheimer\u2019s disease (AD), which is characterized by amyloid-\u03b2 and tau accumulation and lipid peroxidation. This systematic review aimed to evaluate preclinical evidence for DMF as a potential therapeutic agent in AD models through Nrf2 activation. A comprehensive literature search of PubMed and Scopus (last search: December 2025) identified in vitro, in vivo, and combined preclinical studies assessing DMF in AD models. Studies were screened using predefined inclusion and exclusion criteria, and methodological quality was assessed using established tools. Results were synthesized narratively. Eighteen studies were ultimately included in the analysis. Across the included studies, DMF consistently activated the Nrf2 pathway, enhancing antioxidant and anti-inflammatory gene expression. DMF treatment reduced amyloid-\u03b2 and tau protein levels, mitigated oxidative stress, and improved cognitive performance in animal models. However, the evidence is limited by heterogeneity in experimental models and methodological variability. In conclusion, preclinical evidence suggests DMF is a promising candidate for AD treatment by targeting oxidative stress and neuroinflammation via Nrf2 activation. Further preclinical studies, particularly on ferroptosis mechanisms, and well-designed clinical studies are warranted to clarify its full therapeutic potential. This review was not registered and the authors received no funding.<\/jats:p>","DOI":"10.3390\/ijms27104227","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:49:09Z","timestamp":1778572149000},"page":"4227","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Emerging Role of Dimethyl Fumarate in Alzheimer\u2019s Disease\u2014A Systematic Review of Available Preclinical Studies"],"prefix":"10.3390","volume":"27","author":[{"given":"Maria","family":"Mouaimi","sequence":"first","affiliation":[{"name":"Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia 2408, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athanasios","family":"Metaxas","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia 2408, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4176-8425","authenticated-orcid":false,"given":"Malamati","family":"Kourti","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia 2408, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Twarowski, B., and Herbet, M. 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