The Emerging Role of Dimethyl Fumarate in Alzheimer’s Disease—A Systematic Review of Available Preclinical Studies

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's disease (AD), which is characterized by amyloid-β 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 identified in vitro, in vivo, and combined preclinical studies assessing DMF in AD models. Studies were screened using predefined inclusion and exclusion criteria, with quality assessment and flow chart analysis applied. Eighteen studies were ultimately included in the analysis. Results consistently demonstrated that DMF activates the Nrf2 pathway, enhancing antioxidant and anti-inflammatory gene expression. DMF treatment reduced amyloid-β and tau protein levels, mitigated oxidative stress, and improved cognitive performance in animal models. 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, as well as well-designed clinical studies are warranted to clarify its full therapeutic potential.