Traditional Chinese medicine for Alzheimer's disease: pathological mechanisms and multi-target interventions

Alzheimer's disease (AD) is a progressive neurodegenerative disorder driven by multiple interconnected pathological mechanisms. This narrative review systematically searched major biomedical databases for relevant literature published between 2015 and 2026, using predefined keywords combined with manual supplementary searches. Two independent reviewers performed a qualitative screening based on relevance, involving the iterative review of titles, abstracts, and full texts. A targeted selection of representative, high-quality studies centered on TCM and AD pathogenesis/mechanisms was then conducted. Ultimately, studies were included in the narrative review for the mechanistic synthesis of TCM against AD. This review summarizes seven core AD mechanisms, including the Aβ cascade, Tau abnormalities, Neuroinflammation, Regulated cell death, Synaptic plasticity impairment, Gut microbiota-brain axis imbalance, and Oxidative stress, and critically discusses the multi‑target interventions of TCM via key molecules such as GSK-3β, BACE1, SIRT1, NF‑κB, NLRP3, PINK1/Parkin, AMPK, BDNF, PSD‑95, and the Nrf2/HO‑1 pathway. GSK‑3β and NF‑κB act as central hubs linking Aβ/Tau pathology to neuroinflammation, while AMPK, SIRT1, and Nrf2/HO‑1 regulate metabolic and redox homeostasis, PINK1/Parkin control mitophagy, and BDNF/PSD‑95 determine synaptic integrity. TCM's therapeutic superiority lies in its simultaneous modulation of this entire hierarchical network, representing a multi‑target strategy that conventional single‑target drugs cannot replicate. By concurrently modulating these distinct yet interacting nodes, TCM establishes a synergistic therapeutic network that reduces Aβ deposition, attenuates Tau hyperphosphorylation, and mitigates neuronal damage, offering a novel direction for future AD research.