TITLE:
Research Progress on the Pathogenesis of Alzheimer’s Disease
AUTHORS:
Zhilian Li, Junlong Wang
KEYWORDS:
Alzheimer’s Disease, β-Amyloid, Tau Protein, Neuroinflammation, Systemic Imbalance
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.14 No.5,
May
8,
2026
ABSTRACT: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia in the elderly. Currently, its pathogenesis is no longer confined to traditional theories but instead exhibits the characteristics of a complex network involving multi-factorial and multi-level interactions. Traditional research has long focused on the classic pathological hypotheses of β-amyloid (Aβ) deposition and Tau protein hyperphosphorylation. However, the pathogenesis of Alzheimer’s disease (AD) involves more extensive systemic imbalances, indicating that its pathology has transcended the classical pathways of Aβ and Tau proteins. It manifests as a widespread and interconnected network of functional dysregulation at molecular, cellular, and systemic levels, encompassing multiple domains such as protein homeostasis disruption, metabolic pathway disturbances, neuroimmune inflammation, cerebrovascular dysfunction, and gut-brain axis dysregulation. Therefore, therapeutic strategies targeting a single target often yield suboptimal outcomes. Current studies have revealed that core molecular pathology does not exist independently from emerging mechanisms such as neuroinflammation, metabolic dysfunction, vascular impairment, and gut microbiota dysbiosis. Instead, these factors jointly drive the pathological progression of AD through complex interactions. This review aims to systematically integrate recent advances from molecular and cellular levels to the systemic level, elucidating the specific patterns by which these mechanisms intertwine and amplify each other. By doing so, it seeks to uncover the systemic nature of AD pathology and provide a solid theoretical basis for shifting towards multi-targeted, systemic intervention strategies in the future.