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  • Title: Effects of alcohol intake on cognitive function and β-amyloid protein in APP/PS1 transgenic mice.
    Author: Gong YS, Hou FL, Guo J, Lin L, Zhu FY.
    Journal: Food Chem Toxicol; 2021 May; 151():112105. PubMed ID: 33737111.
    Abstract:
    To investigate the effects of alcohol intake on cognitive function and β-amyloid protein (Aβ) in APP/PS1 double-transgenic mice with Alzheimer's disease (AD). Sixty APP/PS1 transgenic male mice were randomized into seven groups: control group, 0.5% alcohol group, 1% alcohol group, 2% alcohol group, 3% alcohol group, and 4% alcohol group, with 10 non-transgenic B6C3F1 mice of the same genetic background as the negative control group. All mice were pair-fed a liquid diet containing alcohol before assessment of learning and memory using the Y-maze test, and of Aβ content and related enzyme activity on them. Immunohistochemistry was used to detect the expression of Aβ1-42, Aβ1-40, and β-amyloid precursor protein (β-APP) in the cerebral cortex. 3%, and 4% alcohol intake significantly impaired the learning and memory abilities. 2%, 3%, and 4% alcohol groups indicated a remarkable change in Aβ1-42 content, α-secretase and γ-secretase activities in the hippocampus, and β-APP in the cortex; 3% and 4% alcohol groups showed a significant increase in Aβ1-42 content, β-site amyloid cleavage enzyme 1 (BACE1) activity, and a significant decrease in α-secretase activity in the hippocampus or cortex; 2% and 3% alcohol groups showed a significant increase in Aβ1-40 content in the hippocampus or cortex; and 2%, 3%, and 4% alcohol groups showed an increase in the expression of Aβ1-42, Aβ1-40, and β-APP in the cortex; 1% alcohol groups showed a significant decline in the levels of Aβ1-42, Aβ1-40, β-APP, and BACE1 activity in the hippocampus, and γ-secretase activity in the hippocampus and cortex, and 1% alcohol group showed a significant increase of α-secretase activity in the hippocampus. Besides, 0.5% alcohol showed statistically significant effects on the reduction of BACE1 and γ-secretase activities in the hippocampus. Long-term intake of high-dose alcohol can induce cognitive deficits and improve the activity of β-APP decomposition-related enzymes, increase Aβ content and deposition, and initiate AD progression, while long-term intake of low-dose alcohol can antagonize excessive production of Aβ and slow down AD progression.
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