IntroductionAlzheimer's disease is a common neurodegenerative disease worldwide. 1,2 The most important cause mentioned was the accumulation of beta-amyloid (Aβ) fibril in the central nervous system (CNS). 3 Actually disruption in Aβ homeostasis can lead to the accumulation of Aβ fibrils as plaques in the brain. 4,5 These plaques can be detected by microglia receptors and finally activate signal cascades into microglia that lead to the release of inflammatory factors from microglia. 6,7 So, in brain of patients with Alzheimer's disease, there is a widespread neuroinflammation that can lead to neuronal apoptosis and brain atrophy. 8 The deposition of Aβ protein is a prominent pathological hallmark of brains affected by Alzheimer's disease. For this reason, the inhibition of Aβ production, prevention of Aβ fibril formation and accumulation, destabilization of pre-formed Aβ are considered as attractive therapeutic methods for the treatment of Alzheimer's disease. 9,10 Many animal and clinical studies showed that curcumin as the main constituent of turmeric spice is an effective ingredient in reducing Aβ plaques in the brain models of Alzheimer's disease. 11,12 Curcumin is well-known as an anti-inflammation and anti-oxidant ingredient. 13 It is a lipophilic compound that can easily cross the blood-brain barrier and affect Aβ plaque. 13,14 It can destabilize the Aβ fibrils and prevent the accumulation of Aβ polymer. 15,16 Many animal studies indicated that curcumin could alter Aβ metabolism in Alzheimer animal models and improve cognition and spatial memory. [17][18][19] But in clinical studies there is controversial results about its effects on Aβ clearance and metabolism. 20,21 For this purpose, we aimed to review the studies which have been done in this area on the effects of curcumin on Aβ 1-40 plasma level in clinical studies to find how curcumin affects Aβ metabolism. Methods Search StrategyWe performed a systematic review and meta-analysis on three randomized clinical trial (RCTs) and one pilot study that assessed the effect of curcumin on Aβ plasma level in Alzheimer's disease. For this purpose, we searched PubMed and Scopus databases up to December 2020, using the following search terms: (curcumin OR diferuloylmethane OR curcuminoids OR turmeric OR "Indian saffron") AND ("Alzheimer disease" OR "Alzheimer's disease" OR "Alzheimer Syndrome" OR "Senile Dementia") AND (amyloid OR "Beta amyloid" OR Aβ) AND (Intervention OR "controlled trial" OR randomized OR random OR randomly OR placebo OR "clinical trial" OR trial OR "randomized controlled trial"