Effects of alcohol intake on cognitive function and β-amyloid protein in APP/PS1 transgenic mice

To investigate the effects of alcohol intake on cognitive function and beta-amyloid protein (A beta) 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 A beta content and related enzyme activity on them. Immunohistochemistry was used to detect the expression of A beta(1-42), A beta(1-40), and beta-amyloid precursor protein (beta-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 A beta(1- 42) content, alpha-secretase and.-secretase activities in the hippocampus, and beta-APP in the cortex; 3% and 4% alcohol groups showed a significant increase in A beta(1- 42) content, beta-site amyloid cleavage enzyme 1 (BACE1) activity, and a significant decrease in a-secretase activity in the hippocampus or cortex; 2% and 3% alcohol groups showed a significant increase in A beta(1- 40) content in the hippocampus or cortex; and 2%, 3%, and 4% alcohol groups showed an increase in the expression of A beta(1-42), A beta(1- 40), and beta-APP in the cortex; 1% alcohol groups showed a significant decline in the levels of A beta(1-42), A beta(1-40), beta-APP, and BACE1 activity in the hippocampus, and.-secretase activity in the hippocampus and cortex, and 1% alcohol group showed a significant increase of a-secretase activity in the hippocampus. Besides, 0.5% alcohol showed statistically significant effects on the reduction of BACE1 and.-secretase activities in the hippocampus. Long-term intake of high-dose alcohol can induce cognitive deficits and improve the activity of beta-APP decomposition-related enzymes, increase A beta content and deposition, and initiate AD progression, while long-term intake of low-dose alcohol can antagonize excessive production of A beta and slow down AD progression.