Objective: We aimed to assess the safety and efficacy of anti-tau monoclonal antibodies in treating Alzheimer’s Disease (AD).

Background: AD is a neurodegenerative disorder characterized by beta-amyloid plaques and tau protein tangles, leading to cognitive and behavioral impairment. Although no cure exists, monoclonal antibodies have been developed as potential therapies. Initially, treatments targeted beta-amyloid, but more recent approaches focus on tau pathology.

Design/Methods: We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCT) comparing anti-tau monoclonal antibodies to placebo in AD patients. The efficacy outcomes were the change in Clinical Dementia Rating Sum of Boxes (CDR-SB) in the overall population and early-stage AD, and the reduction of tau protein in cerebrospinal fluid (CSF). Safety outcomes included adverse events (AEs), serious AEs, and discontinuation rates.

Results: After screening 528 articles, 6 RCTs comprising 2145 participants (56.1% female) were included. No significant difference was observed in CDR-SB changes for all AD patients (Mean Difference [MD] 0.121; 95% CI -0.10–0.33; p=0.28; I²=0%) or early-stage AD (MD 0.095; 95% CI -0.14–0.33; p=0.42; I²=0%). CSF tau levels were significantly reduced in the intervention group. Anti-tau therapies did not increase the risk of any AE (Relative Risk [RR] 1.01; 95% CI 0.96–1.05; p=0.77; I²=46%), serious AEs, nor did they lead to higher discontinuation rates.

Conclusions: Our results did not demonstrate a therapeutic benefit of anti-tau monoclonal antibodies in slowing disease progression as measured by CDR-SB, although they showed no increased risk of adverse events and are a safe therapy. Further research is needed to evaluate their long-term impact.