Metabolic syndrome and Alzheimer's disease: Mechanistic links and precision prevention (Review)

Metabolic syndrome (MetS) is associated with increased risk of Alzheimer's disease (AD), however, the majority of previous studies regard MetS as an isolated risk factor and focus on single pathways, lacking systematic understanding of combined effects among multiple metabolic components. The present review systematically summarizes the multifaceted mechanisms by which MetS promotes AD pathology, including insulin resistance and cerebral energy dysregulation, oxidative stress and mitochondrial dysfunction, neuroinflammation and glial cell activation, vascular dysfunction and dysregulation of the renin‑angiotensin system, as well as the central convergent signaling pathway involving glycogen synthase kinase‑3β. The present review further highlights emerging regulatory mechanisms involving the gut‑brain axis, epigenetic reprogramming, sex differences and hormonal effects and senescent microenvironment. By emphasizing the peripheral‑central crosstalk and interactive amplification of MetS components, the present review aimed to position AD as a central manifestation of systemic metabolic disorders in the brain and propose a multi‑domain precision strategy integrating lifestyle intervention, metabolic drug repurposing, gut microbiota regulation, anti‑aging therapy and biomarker‑guided subtype classification for intervention against MetS‑associated AD.