Deciphering the Multifaceted Pathophysiological Mechanisms Underlying Alzheimer’s Disease: Expanding Beyond Amyloid-Centric and Tau-Centric Paradigms in the Context of the Neurodegenerative Continuum

Abstract

Alzheimer’s disease (AD) is a complex neurodegenerative disorder traditionally associated with amyloid-β (Aβ) plaques and tau tangles. However, emerging evidence suggests a broader pathophysiological spectrum beyond the amyloid-centric and taucentric hypotheses. This review explores alternative mechanisms contributing to AD, including neuroinflammation, oxidative stress, mitochondrial dysfunction, gut-brain axis dysregulation, cerebrovascular impairments, and metabolic dysregulation