Hydroxytyrosol mildly improve cognitive function independent of APP processing in APP/PS1 mice

Scope: Olive products, the hallmark of Mediterranean diet, are associated with reduced risk of mild cognitive impairment and Alzheimer's disease (AD). We and other groups have shown that hydroxytyrosol (HT), a bioactive compound of olive products, ameliorates oxidative stress, mitochondrial dysfunction, and neural toxicity. However, whether HT in Mediterranean diet acts as a functional ingredient in delaying AD pathogenesis remains unclear. Methods and results: In the present study, APP/PS1 mice, an animal model of AD, were administrated for 6 months with 5 mg/kg/day of HT, a comparable level of HT in daily Mediterranean diet. HT improved electroencephalography activity and marginally benefited cognitive behavior of transgenic mice. In addition, HT treatment ameliorated mitochondrial dysfunction, reduced mitochondrial carbonyl protein, enhanced superoxide dismutase 2 expression, reversed the phase 2 enzyme system and reduced the levels of brain inflammatory markers, but had no effect on brain β-amyloid (Aβ) accumulation in APP/PS1 mice. Conclusions: These results suggest that HT may represent as a functional ingredient in Mediterranean diet in ameliorating AD-involved neuronal impairment via modulating mitochondrial oxidative stress, neuronal inflammation, and apoptosis without affecting APP processing.