Chapter 17: Tau-targeting Therapeutic Strategies for Alzheimer's Disease Check Access

Abnormal tau aggregation and accumulation in the form of intracellular neurofibrillary tangles (NFT) and paired helical filaments (PHFs) are among the hallmarks of Alzheimer's disease (AD) pathology. Tau undergoes different aberrant post-translational modifications (PTMs), mainly phosphorylation, glycosylation and acetylation, which trigger tau pathology. The multifactorial nature of AD and the failures encountered in amyloid targeted drug developments have prompted researchers to search for alternate tangible disease routes and drug targets. In the last two decades, drug discovery targeting tau pathology has shown many promising candidates, which are in different phases of clinical trials. In this chapter, we discuss various small molecules developed to modulate the abnormal PTMs to halt tau pathology. Small molecule and peptide based therapeutic candidates developed to modulate various aberrant PTMs, tau aggregation inhibitors and microtubule stabilizers are discussed. Over the last decade, immunotherapy has been explored to ameliorate tau pathology in AD, and antibody-based therapeutics have reached clinical trials with a promising outlook. Gene therapy has been explored to target tau pathology with reasonable success, while further studies are required to establish the feasibility of this strategy. We describe the success and challenges of tau-targeted immunotherapy and gene therapies for AD.