Alzheimer’s Disease (AD) accounts for 60–70% of global dementia cases, affecting around 50 million people worldwide, with incidence doubling every five years after age 60. By 2040, dementia is projected to impact 81.1 million people globally. AD is characterized by amyloid-β plaques and neurofibrillary tangles of Tau protein, leading to mitochondrial dysfunction, oxidative stress, disrupted brain glucose homeostasis, neuroinflammation, and neuron death. AD is influenced by genetic and external factors, with key risk factors including aging, gender, lifestyle habits, and metabolic disorders. While there is no cure, preventive and therapeutic nutritional interventions, particularly those targeting modifiable lifestyle factors, show promise.

The olive tree (Olea europaea) products contain bioactive compounds like polyphenols, oleuropein, and hydroxytyrosol, which have potent antioxidant and anti-inflammatory properties. Olive industry by-products, such as pomace, leaves, and wastewater, are now being utilized for their potential in food, pharmaceuticals, and cosmetics. These by-products can be transformed into health supplements. Technological advances allow the extraction of valuable phenolic compounds from wastewater, aligning with circular economy principles.

Despite the promising bioactive compounds in olives, significant knowledge gaps remain regarding their mechanisms of action and optimal formulations. This Research Topic aims to consolidate global trends and insights on the health benefits of olive-derived bioactive metabolites. We invite original research and review articles exploring the therapeutic potential of these compounds, including pre-clinical and clinical studies on their role in AD. The goal is to deepen the understanding of olive-derived bioactive metabolites and advance nutraceutical-based therapies. Submissions may include, but are not limited to, the following themes:

• Identification and characterization of bioactive compounds: detailed analysis and profiling of olive-derived metabolites using advanced chromatographic and spectroscopic techniques. Evaluation of bioavailability and metabolic pathways in the human body.

• Mechanisms of action: investigation into how olive-derived metabolites exert neuroprotective effects, including modulation of oxidative stress, reduction of neuroinflammation, and inhibition of amyloid-beta aggregation.

• Preclinical studies: conducting in silico/molecular docking studies. In vitro studies with neuronal cell cultures to assess protective effects against neurotoxic insults relevant to Alzheimer’s pathology. Implementation of in vivo studies in animal models to evaluate therapeutic efficacy and safety profiles of olive-derived compounds.

• Clinical implications: examination of existing clinical data and potential integration of olive-derived metabolites into dietary interventions or as nutraceutical supplements for Alzheimer’s prevention and management. Design and initiation of clinical trials to evaluate efficacy, dosage, and long-term effects in human subjects with mild cognitive impairment or early-stage Alzheimer’s disease.

• Synergistic effects and combinatorial therapies: Investigation of potential synergistic effects of olive-derived metabolites with existing Alzheimer’s treatments or other dietary supplements. Assessment of combinatorial approaches to enhance overall therapeutic outcomes.

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Frontiers in Nutrition

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Impact