Tau and Amyloid beta causes microglial activation in Alzheimer's disease.

Abstract

Alzheimer's disease is a neurodegenerative condition characterized by the accumulation of hyperphosphorylated Tau in neurofibrillary tangles and amyloid-beta plaques. Tau, a microtubule-associated protein essential for neuronal stability, detaches from microtubules upon hyperphosphorylation, forming aggregates that disrupt neuronal function. Amyloid beta (Aβ) plaques act as upstream triggers, promoting Tau hyperphosphorylation and activating glial cells, particularly microglia and astrocytes. While these glial cells initially serve protective roles, their chronic activation leads to neuroinflammation, oxidative stress, and neuronal damage. Calcium dysregulation further exacerbates AD pathology by contributing to Tau hyperphosphorylation, mitochondrial dysfunction, and Aβ generation. This review highlights the intricate interplay between Tau, Aβ, and glial cells in the progression of AD, emphasizing both their protective and detrimental roles. It also explores the therapeutic implications of targeting these pathways, including modulating Tau phosphorylation, enhancing Aβ clearance, regulating glial activation, restoring calcium homeostasis, and preserving mitochondrial function. By addressing these multifaceted processes, this review underscores the potential for novel therapeutic strategies to slow or manage the progression of AD, ultimately improving patient outcomes.