Nazli, D.Ipekgil, D.Poyraz, Y.K.Can, K.Okmen, I.Turhanlar-Sahin, E.Ozhan, G.2026-02-252026-02-2520260360-4012https://doi.org/10.1002/jnr.70119https://hdl.handle.net/11147/18967Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and behavioral alterations. The pathogenesis of AD involves the accumulation of amyloid-beta (Aβ) plaques and the hyperphosphorylated tau proteins, which disrupt neuronal function and trigger neuroinflammation. This study explores the therapeutic potential of epigallocatechin gallate (EGCG) and punicalagin (PU) in mitigating Aβ-induced toxicity using an adult zebrafish model of AD. Our results demonstrate that the EGCG + PU combination significantly reduces Aβ accumulation, protects against cellular damage, suppresses acetylcholinesterase (AChE) activity, and normalizes the expression of amyloidogenic and AD-related genes. Additionally, EGCG + PU treatment alleviates neuroinflammation by suppressing glial activation, including reductions in L-plastin and proinflammatory cytokine expression, while promoting neuronal recovery through mechanisms of neurogenesis and neuroprotection. Notably, the combination treatment restored neuronal density and improved behavioral outcomes by alleviating anxiety- and aggression-like behaviors associated with Aβ toxicity. These results underscore the synergistic neuroprotective effects of EGCG + PU, highlighting their potential as a novel therapeutic approach for mitigating the pathological, behavioral, and inflammatory aspects of AD. © 2026 Wiley Periodicals LLC.eninfo:eu-repo/semantics/closedAccessAlzheimer’s DiseaseNeurogenesisNeuroinflammationNeuroprotectionZebrafishArticle2-s2.0-10502973406610.1002/jnr.70119