Multifactorial Pathogenesis, Diagnosis, and Therapeutic Strategies in Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) has traditionally been explained by the amyloid cascade hypothesis as its core mechanism. However, the limitations of single-target therapies reflect that AD cannot be simply explained by a linear pathogenic mechanism. This review examines key mechanisms including the Aβ-tau axis, neuroinflammation, genetic factors, and mitochondrial metabolic abnormalities, proposing that AD pathogenesis should instead be modeled as a multifactorial pathological network. Different pathological nodes amplify disease severity collectively, with multiple factors synergistically driving neuronal network dysfunction and cognitive decline. The review also examines trends in blood biomarkers, imaging, and digital metrics, exploring stratified diagnostics and nodetargeted therapies for multifactorial pathogenesis. This model integrates diverse mechanisms into a comprehensive disease network, providing a theoretical foundation for precision medicine.