Alzheimer's Disease: Mechanisms and Therapeutic Advances

ABSTRACT

Alzheimer's disease (AD) is a devastating neurodegenerative condition accompanied by widespread central nervous system damage and complex networked pathogenesis spanning molecular, cellular, and systemic dimensions. Existing studies tend to focus on individual pathological cascades or monotherapeutic approaches, while overlooking the intrinsic crosstalk among protein pathology, neuroinflammation, metabolic dysfunction, and gut–brain axis imbalance, with insufficient systematic integration of nonpharmacological strategies and multifunctional nanoplatforms. Driven by intertwined molecular aberrations, glial dysregulation and systemic metabolic disorders, AD presents profound pathological complexity. Correspondingly, multitarget pharmacotherapy integrated with hierarchical nonpharmacological and nanotherapeutic interventions has achieved substantial progress, exerting synergistic effects on alleviating AD pathological cascades and optimizing overall therapeutic regimens. We comprehensively review current evidence to delineate the mechanistic landscape of AD and update therapeutic advances, including pharmacological agents, multimodal nonpharmacological interventions, and brain‐targeted nanosystems for blood–brain barrier penetration, protein modulation, microenvironment remodeling, and gene editing delivery. This study underscores major research limitations and translational obstacles in therapeutic efficacy, biosafety, and nanomedicine applications. This work emphasizes biomarker‐based early stratification and staged combined interventions, providing novel integrated insights into AD pathogenesis and prospective targeted therapeutic development.