Epicatechin Plus Treadmill Exercise are Neuroprotective Against Moderate-stage Amyloid Precursor Protein/Presenilin 1 Mice

Epidemiological evidence suggests that exercise and dietary polyphenols are beneficial in reducing Alzheimer's disease (AD) risk. In the present study, 8 months old amyloid precursor protein/presenilin 1 (APP/PS1) mice (a moderate pathology phase) were given the green tea catechin (-)-epicatechin delivered orally in the drinking water (50 mg/kg daily), along with treadmill exercise for 4 months, in order to investigate whether the combination can ameliorate the cognitive loss and delay the progression of AD in APP/PS1 transgenic (Tg) mice. At termination, untreated-Tg mice showed elevated soluble amyloid-β (Aβ1-40) and Aβ1-42 levels and deficits in spatial learning and memory, compared with their wild-type littermates. The combined intervention protected against cognitive deficits in the Morris water maze, lowered soluble Aβ1-40 and Aβ1-42 levels in the hippocampus as well as reducing brain oxidative stress. In addition, brain-derived neurotrophic factor proteins wee elevated and Akt/GSK-3/cAMP response element-binding protein signaling was activated in the combination group. Dietary polyphenol plus exercise may exert beneficial effects on brain health and slow the progression of moderate- or mid-stages of AD. Amyloid precursor protein/presenilin 1 transgenic mice showed elevated soluble amyloid-β (Aβ1-40) and Aβ1-42 levels and deficits in spatial learning and memory, compared with their wild-type littermatesOral administration of epicatechin, combined with treadmill exercise for 4 months, could protect against cognitive deficits, and lowered soluble Aβ1-40 and Aβ1-42 levels as well as reducing brain oxidative stressBrain-derived neurotrophic factor proteins were elevated, and Akt/GSK-3/cAMP response element binding protein signaling was activated in the combination groupDietary polyphenol plus exercise might exert beneficial effects on brain health and slow the progression of moderate- or mid-stages of Alzheimer's disease. Abbreviations used: AD: Alzheimer's disease, Tg: APP/PS1 transgenic, BDNF: Brain-derived neurotrophic factor, Aβ: Amyloid-β, APP: Amyloid precursor protein, PS1: Presenilin 1, nTg: Wild-type littermates, IACUC: Institutional Animal Care and Use Committee, GSSG: Glutathione oxidized form, GSH: Glutathione reductase, SOD: Superoxide dismutase, CAT: Catalase, LPO: Lipoperoxidation, CREB: cAMP response element binding protein.