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

BACKGROUND: Epidemiological evidence suggests that exercise and dietary polyphenols are beneficial in reducing Alzheimer's disease (AD) risk. MATERIALS AND METHODS: 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. RESULTS: At termination, untreated-Tg mice showed elevated soluble amyloid-β (Aβ(1–40)) and Aβ(1–42) 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 Aβ(1–40) and Aβ(1–42) 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. CONCLUSIONS: Dietary polyphenol plus exercise may exert beneficial effects on brain health and slow the progression of moderate- or mid-stages of AD. SUMMARY: Amyloid precursor protein/presenilin 1 transgenic mice showed elevated soluble amyloid-β (Aβ(1–40)) and Aβ(1–42) levels and deficits in spatial learning and memory, compared with their wild-type littermates. Oral administration of epicatechin, combined with treadmill exercise for 4 months, could protect against cognitive deficits, and lowered soluble Aβ(1–40) and Aβ(1–42) levels as well as reducing brain oxidative stress. Brain-derived neurotrophic factor proteins were elevated, and Akt/GSK-3/cAMP response element binding protein signaling was activated in the combination group. Dietary 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.