Alzheimer's Disease Pathogenesis: Classic Versus Novel Perspectives

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system characterized by progressive cognitive impairment and behavioral deficits. Its pathogenesis is complex and has not been fully elucidated to date. This review aims to systematically elaborate on the multifactorial pathogenic mechanisms of AD. Traditionally, senile plaques formed by β-amyloid (Aβ) deposition and neurofibrillary tangles caused by hyperphosphorylation of the microtubule-associated protein Tau are regarded as the core pathological features of AD. In recent years, studies have found that microglial dysfunction, gut microbiota dysbiosis, mitochondrial dysfunction, and genetic risk factors all play key roles in the occurrence and progression of AD. These mechanisms are intertwined, forming a complex network that collectively drives neuronal loss and synaptic damage. This article reviews the latest research progress on the aforementioned major mechanisms, aiming to provide a theoretical basis for in-depth understanding of the pathophysiological processes of AD. Finally, based on the understanding of the multi-mechanism network, this article prospects the multimodal therapeutic strategies targeting Aβ, Tau, and neuroinflammation in combination, which may be an important direction for the development of new AD drugs in the future.