Exploring Resveratrol as a Multi-Faceted Therapeutic for Alzheimer’s Disease

Resveratrol shows multi-target, disease‑modifying potential in Alzheimer’s disease, modulating amyloid and tau, attenuating neuroinflammation, and preserving mitochondrial function—positioning it as a candidate for biomarker‑led therapeutic development.

At the molecular level, resveratrol influences amyloid processing by modulating secretase activity and enhancing clearance pathways, and it reduces tau hyperphosphorylation and aggregation through SIRT1‑linked and kinase‑mediated effects. It also attenuates microglial activation and lowers proinflammatory cytokines, while protecting mitochondria and scavenging reactive oxygen species to preserve neuronal energy homeostasis—together creating a plausible disease‑modifying rationale for clinical evaluation.

The principal challenge remains resveratrol’s native pharmacokinetics, which limit CNS exposure and oral bioavailability. Formulation advances are therefore essential to increase brain delivery; approaches under investigation include nanoformulations, prodrugs, liposomal and polymer carriers, CNS‑targeting ligands, and intranasal routes.

Phase II evidence indicates resveratrol is generally safe and tolerable and can produce measurable changes in Alzheimer’s biomarkers. Randomized studies of several months up to a year used CSF Aβ and tau measures, PET imaging, and plasma markers as primary biomarker endpoints; they reported a reassuring safety profile alongside changes in biomarker trajectories, but efficacy signals remain modest and require adequately powered, efficacy‑focused trials.

Practical biomarkers for monitoring include CSF Aβ42 and Aβ42/40 ratios, total and phospho‑tau, neurofilament light (NfL), amyloid and tau PET, and CSF or plasma inflammatory cytokines. Combination strategies worth testing in adaptive, biomarker‑rich designs include add‑on studies with approved anti‑amyloid therapies, adjunctive anti‑inflammatory agents, or metabolic modulators to exploit complementary mechanisms and potential synergy.