Role of tau protein in Alzheimer's disease: The prime pathological player

Abstract

Alzheimer's disease (AD) is a prevalently found tauopathy characterized by memory loss and cognitive insufficiency. AD is an age-related neurodegenerative disease with two major hallmarks which includes extracellular amyloid plaques made of amyloid-β (Aβ) and intracellular neurofibrillary tangles of hyperphosphorylated tau. With population aging worldwide, there is an indispensable need for treatment strategies that can potentially manage this developing dementia. Despite broad researches on targeting Aβ in the past two decades, research findings on Aβ targeted therapeutics failed to prove efficacy in the treatment of AD. Tau protein with its extensive pathological role in several neurodegenerative diseases can be considered as a promising target candidate for developing therapeutic interventions. The abnormal hyperphosphorylation of tau plays detrimental pathological functions which ultimately lead to neurodegeneration. This review will divulge the importance of tau in AD pathogenesis, the interplay of Aβ and tau, the pathological functions of tau, and potential therapeutic strategies for an effective management of neuronal disorders.

Keywords: Alzheimer's disease; Amyloid-β; Hyperphosphorylation; Neurodegeneration; Neurofibrillary tangles; Pathological functions; Tau protein.