A critical appraisal of tau‐targeting therapies for primary and secondary tauopathies. Issue 5 (17th September 2021)

• Record Type: Journal Article
• Authors: Imbimbo, Bruno P.; Ippati, Stefania; Watling, Mark; Balducci, Claudia
• Is Part Of: Alzheimer's & dementia. Volume 18:Issue 5(2022)
• Page Start: 1008
• Page End: 1037
• Publication Date: 2021-09-17
• Subjects: Alzheimer's disease -- amyloid beta -- corticobasal degeneration -- frontotemporal dementia -- frontotemporal lobar degeneration -- N‐truncated‐tau -- oligomeric tau -- phosphorylated tau -- primary tauopathies -- progressive supranuclear palsy -- p‐tau‐181 -- p‐tau‐205 -- p‐tau‐217 -- p‐tau‐231 -- tau; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.12453
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Introduction: Primary tauopathies are neurological disorders in which tau protein deposition is the predominant pathological feature. Alzheimer's disease is a secondary tauopathy with tau forming hyperphosphorylated insoluble aggregates. Tau pathology can propagate from region to region in the brain, while alterations in tau processing may impair tau physiological functions. Methods: We reviewed literature on tau biology and anti‐tau drugs using PubMed, meeting abstracts, and ClnicalTrials.gov. Results: The past 15 years have seen >30 drugs interfering with tau aggregation, processing, and accumulation reaching the clinic. Initial results with tau aggregation inhibitors and anti‐tau monoclonal antibodies have not shown clinical efficacy. Discussion: The reasons for these clinical failures are unclear but could be linked to the clearing of physiological forms of tau by non‐specific drugs. Research is now concentrating efforts on developing reliable translational animal models and selective compounds targeting specific tau epitopes, neurotoxic tau aggregates, and post‐translational tau modifications.