Alzheimer's Disease is a neurodegenerative disease associated with cognitive impairment in mid- and late-life. It is characterized by the formation of senile plaques (containing β-amyloid or Aβ peptide) and neurofibrillary tangles (NFT, composed of hyperphosphorylated Tau protein). Tau normally binds to microtubules, but in its hyperphosphorylated form, it cannot bind properly, leading to microtubule instability, disrupted cellular traffic, synapse loss, cognitive decline, and dementia.
Several processes contribute to the hyperphosphorylation of Tau, including Aβ peptides, impaired glucose metabolism, and inflammation. Aβ peptides are a major component of senile plaques and play a key role in Alzheimer's disease pathogenesis. They result from the amyloidogenic metabolism of amyloid precursor protein (APP) and tend to aggregate into plaques.
Hydroxytyrosol and oleuropein have been found to inhibit the fibrillization of Tau protein, reducing intraneuronal and glial lesions. They also prevent the aggregation of Aβ peptides, including Aβ1–42 oligomers, in neuroblastoma cells and mouse models of Alzheimer's disease. This prevention is associated with improvements in spatial and associative memory. These compounds have additional beneficial effects, such as preventing insulin secretion issues, amylin deposition, and α-synuclein aggregation. They also promote autophagy, a cellular process for removing dysfunctional components, which is relevant to Alzheimer's disease.
Hydroxytyrosol has been shown to induce mitochondrial generation and fusion, which can counteract mitochondrial dysfunction seen in Alzheimer's disease. It helps in reducing the accumulation of reactive oxygen species (ROS) and the impairment of mitochondrial function.
Hydroxytyrosol and tyrosol have been found to protect against cell death and inflammation caused by Aβ oligomers in neuroblastoma cells. They also restore insulin signaling in astrocytes, which is important for neuronal functioning.
In summary, hydroxytyrosol and oleuropein appear to have several potential beneficial effects on the pathology and symptoms of Alzheimer's disease, including inhibiting Tau and Aβ aggregation, promoting autophagy, improving mitochondrial function, and providing neuroprotection. However, the dosage and timing of treatment may be critical factors in achieving these effects. Further research is needed to fully understand their therapeutic potential for Alzheimer's disease.
