Translational Feasibility of Curcumin for Treatment of Alzheimer's Disease: A Critical Appraisal of Clinical Challenges.

The absence of robust and effective treatments for Alzheimer's disease remains a major challenge in modern medicine. As one of the leading causes of death, its increasing prevalence and complex chronic pathogenesis impose a substantial societal and healthcare burden, intensifying the need for effective therapeutic strategies. Current treatments remain limited, with minimal impact on cognitive decline in symptomatic patients. Curcumin, the bioactive ingredient in turmeric, has taken precedence over other natural products due to its potent antioxidative and anti-inflammatory properties. Numerous publications have extensively reported on the therapeutic effect of curcumin in animal models of Alzheimer's disease. However, no curcumin formulation has demonstrated consistent clinical efficacy against Alzheimer's or other neurodegenerative diseases to date. Over the years, many critics have argued that curcumin's undesirable chemical properties, mainly low bioavailability and rapid metabolism, pose significant barriers to its therapeutic use to target the brain. Considerable funding and research effort on emerging technologies such as nanoparticles and intranasal delivery continue to drive curcumin preclinical and clinical trials, prompting reflection on the rationale for continued investment. This narrative review critically dissects this disconnect, arguing that many purported benefits remain insufficiently substantiated, and identifying important opportunities where future research may hold promise for an effective treatment.