Efficacy and Safety of Anti-Tau Drugs for Alzheimer’s Disease: A Systematic Review and Network Meta-Analysis - 24/10/26

Doi : 10.1016/j.tjpad.2026.100693

Yuetao Hu ^{^{†
Yuetao Hu, Yuning Cheng, and Yanqu Su contributed equally to this work.}}, Yuning Cheng ^{^{†
Yuetao Hu, Yuning Cheng, and Yanqu Su contributed equally to this work.}}, Yanqu Su ^{^{†
Yuetao Hu, Yuning Cheng, and Yanqu Su contributed equally to this work.}}, Zeming Han, Xiaohan Shen, Hantian Hu, Qi Wang, Siqi Wan, Hanyu Li, Nan Zhang ^⁎

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China

^⁎ Corresponding author: Nan Zhang, MD, PhD, Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, China. Department of Neurology Tianjin Neurological Institute Tianjin Medical University General Hospital 154 Anshan Road Tianjin 300052 China

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Highlights

●	Anti-tau therapies significantly reduce cerebrospinal fluid p-tau and t-tau levels.
●	Anti-tau therapies do not significantly improve cognitive and functional outcomes.
●	MAPT _Rx and nicotinamide improve cognitive function with the greatest efficacy.
●	Meta-regression shows age is associated with t-tau reduction post anti-tau therapy.
●	Anti-tau drugs are safe, except for a higher risk of injection-site reactions.

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Abstract

Objective

To evaluate and compare the effects of different anti-tau drugs on clinical and biological outcomes in patients with Alzheimer’s disease (AD).

Methods

PubMed, Cochrane Library, and Embase databases were searched for identifying randomized, controlled clinical trials from inception to December 2025.

Results

Twelve high-quality studies with 11 drugs were evaluated. Systematic meta-analysis did not demonstrate significant efficacy of anti-tau drugs in preventing cognitive and functional declines or clearance of tau deposition on PET. However, effects in reducing levels of p-tau (SMD=-0.48, 95% CI: -0.73 to -0.22, P < 0.01) and t-tau (SMD=-0.69, 95% CI: -0.94 to -0.45, P < 0.01) in the cerebrospinal fluid were observed. Network analysis revealed that MAPT _Rx and nicotinamide ranked highest for improving cognitive function, and gosuranemab ranked highest for tau biomarker changes.

Conclusion

The current findings highlight the disease-modifying potential of anti-tau therapies for AD, although clinical benefit is limited. The observed reductions in CSF tau biomarkers and the favourable safety profile of current anti-tau therapies suggest promising therapeutic potential for the treatment of AD. However, the clinical value of anti-tau therapies should be confirmed in adequately powered phase III trials with biomarker-enriched populations.

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Keywords : Alzheimer’s disease, Anti-tau drugs, Network meta-analysis, Meta-regression