Chapter 3. Alzheimer's Disease Pathology: A Tau Perspective

Alzheimer's disease leads to gradual memory loss and impaired cognition. The accumulation of the misfolded proteins amyloid-β and Tau play a cardinal role in the pathology and disease progression. The aggregation and accumulation of microtubule-associated protein Tau plays a pivotal role in AD. In addition to its role in microtubule dynamics, Tau plays an important role in maintaining synapses, neuritic extensions as well as neuronal architecture as a whole. The Tau pathology in AD is attributed to various causes like mutations and post-translational modifications (PTMs). Tau is a phosphoprotein and relies on phosphorylation for its cellular functions. The aberrant phosphorylation drives Tau into pathogenic transition leading to its misfolding, aggregation and accumulation. These events have various implications on the cellular machinery including impairment of degradation pathways, induction of oxidative stress and neuronal death. Thus, Tau has emerged as a crucial biomarker in the diagnosis of AD as it correlates with the disease progression. The technological advancement has led to the development of less-invasive methods to detect femtomolar concentrations of Tau in body fluids. Additionally, the therapeutic advancement in Tau-targeted molecules is gaining success in preliminary observations in clinical trials. Thus, here we have addressed the implications of Tau pathology in AD and its importance in disease diagnosis and therapeutic intervention.