International Journal of Molecular Sciences · 10 authors, 10 centres
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This narrative review synthesizes preclinical evidence that olive leaf polyphenols, such as oleuropein and hydroxytyrosol, may modulate molecular pathways implicated in Alzheimer's disease, including amyloid-beta aggregation, tau phosphorylation, oxidative stress, and neuroinflammation. The main limitation is that most evidence comes from in vitro and animal models, with very limited human data, so clinical relevance for humans remains indirect and unconfirmed.
Alzheimer’s disease (AD) is characterized by amyloid-beta (Aβ) plaque aggregation, tau neurofibrillary tangles, oxidative stress, and neuroinflammation. Evidence from preclinical models shows OL extracts and their compounds can reduce Aβ fibrillization, inhibit enzymes like BACE-1, AChE, and BChE, and modulate tau phosphorylation. In vitro and animal studies suggest OL supplementation may attenuate neuroinflammation by downregulating NF-κB, NLRP3, and cytokines like IL-1β, and reduce oxidative stress by activating the Nrf2 pathway and increasing antioxidant enzymes. Some studies in AD mouse models (e.g., 5xFAD, APPswe/PS1dE9) report reduced Aβ deposits and improved memory function. However, the review notes limited direct evidence for behavioral improvements in AD models and highlights the need for more human clinical trials. The phytochemical profile of OL is variable due to factors like cultivar and extraction method, and bioavailability studies in humans are sparse but indicate metabolites are detectable in plasma and urine. Overall, the data support a potential role for OL polyphenols in targeting multiple AD-related pathways, but translation to human therapy remains speculative.
