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



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.



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.
Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Yunhua
Y
Peng
Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Chen
C
Hou
Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Ziqi
Z
Yang
Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Caixia
C
Li
Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Liyan
L
Jia
Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Jing
J
Liu
Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Ying
Y
Tang
Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Le
L
Shi
School of Biomedical engineering, Third Military Medical University, Chongqing, China.
Yongqin
Y
Li
Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Jiangang
J
Long
Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Jiankang
J
Liu
D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D038441:Diet, Mediterranean; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D031658:Olea / Q000737:chemistry*; D018384:Oxidative Stress; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology
D016229:Amyloid beta-Peptides; C005975:3,4-dihydroxyphenylethanol; D010626:Phenylethyl Alcohol
Alzheimer's disease; Cognitive function; Hydroxytyrosol; Inflammation; Mediterranean diet; Oxidative stress