Neuropharmacological links Between Diabetes and Alzheimer's Disease: Molecular crosstalk and Therapeutic Potential of Flavonoids

Objectives: To analyze the molecular and neuropharmacological links between Diabetes and Alzheimer’s Disease and to evaluate the therapeutic potential of flavonoids in diabetes-associated Alzheimer’s disease (DAAD). Material and Method: Using indexed biomedical literature, a narrative evaluation of experimental, preclinical, and clinical studies addressing insulin resistance, oxidative stress, neuroinflammation, amyloid pathology, and flavonoid-mediated neuroprotection in DM and AD was carried out. Result: DM and AD share comparable pathophysiological pathways including insulin resistance, mitochondrial dysfunction, oxidative stress, chronic inflammation, advanced glycation end products (AGEs), and decreased SIRT1/AMPK signalling. Brain insulin resistance relates to amyloid-β build up and tau hyperphosphorylation. In experimental models, flavonoids including quercetin, rutin, kaempferol, genistein, luteolin, naringenin, and hesperidin demonstrate insulin-sensitizing, anti-inflammatory, anti-amyloidogenic, and anticholinesterase properties. Conclusion: Flavonoids are prospective multi-target therapeutic agents for DAAD, as they modulate shared molecular pathways of DM and AD. Nevertheless, in order to verify the efficacy, safety, and optimal administration strategies, well-designed clinical trials are necessary.