Tau immunotherapies: Lessons learned, current status and future considerations

• Published in: Neuropharmacology 2020-09, Vol.175, p.108104-108104, Article 108104
• Main Authors: Sandusky-Beltran, L.A., Sigurdsson, E.M.
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - immunology; Alzheimer Disease - therapy; Animals; Antibodies - therapeutic use; Clinical Trials as Topic; Humans; Immunotherapy; tau Proteins - immunology; Tauopathies - immunology; Tauopathies - therapy
• ISSN: 0028-3908; 1873-7064; 1873-7064
• DOI: 10.1016/j.neuropharm.2020.108104

The majority of clinical trials targeting the tau protein in Alzheimer's disease and other tauopathies are tau immunotherapies. Because tau pathology correlates better with the degree of dementia than amyloid-β lesions, targeting tau is likely to be more effective in improving cognition than clearing amyloid-β in Alzheimer's disease. However, the development of tau therapies is in many ways more complex than for amyloid-β therapies as briefly outlined in this review. Most of the trials are on humanized antibodies, which may have very different properties than the original mouse antibodies. The impact of these differences are to a large extent unknown, can be difficult to decipher, and may not always be properly considered. Furthermore, the ideal antibody properties for efficacy are not well established and can depend on several factors. However, considering the varied approaches in clinical trials, there is a general optimism that at least some of these trials may provide functional benefits to patients suffering of various tauopathies. This article is part of the special issue entitled ‘The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders’. •Many clinical trials for Alzheimer's disease are tau immunotherapies.•The development of tau immunotherapies is complex as outlined in this review.•Barriers to success and suggestions for future clinical trials are discussed.•An up-to-date status of current clinical trials is also provided.