Background Aluminum is an important environmental risk factor for Alzheimer's disease, and ApoE4 gene is an important genetic determinant of Alzheimer's disease. In recent years, how aluminum and ApoE4 gene lead to learning and memory impairment has drawn wide attention. Aluminum and ApoE4 gene play important roles in β-amyloid protein (Aβ) clearance and neuronal synaptic plasticity, which needs further exploration.

Objective This experiment explores the effects of aluminum and ApoE4 gene on the content of Aβ and the content of low density lipoprotein family, such as apolipoprotein E receptor 2 (ApoER2), in mice.

Methods Sixteen wild type C57BL/6 mice and 16 transgenic mice with human ApoE4 gene were included in this study. Both types of mice were randomly divided into aluminum exposure group40 μmol·kg^-1 Al(mal)₃ and control group (normal saline) with 8 mice in each group. Intraperitoneal injection of Al(mal)₃ solution was successively performed for 5 d and rested for 2 d, and the exposure time was 60 d in total. The learning and memory ability of mice was detected with Morris water maze; the synaptic plasticity in CA1 area of hippocampus was detected with Golgi staining; the protein expressions of ApoER2, low density lipoprotein receptor-related protein 1 (LRP1), very low density lipoprotein receptor (VLDLR s), and amyloid protein precursor (APP) in hippocampus were detected by Western blotting; and the levels of Aβ40 and Aβ42 proteins in hippocampus was detected by Elisa.

Results The results of Morris water maze showed that the escape latencies of the C57BL/6 control group, the C57BL/6 aluminum group, the ApoE4 control group, and the ApoE4 aluminum group on the first day after the end of exposure were (48.56±18.31), (46.77±19.91), (45.13±19.07), and (46.81±18.04) s, respectively; on the fifth day after the end of exposure, the results were decreased to (19.43±13.28), (27.03±17.47), (21.27±20.17), and (30.06±20.02) s, respectively. The results of analysis of variance showed that the differences of escape latency between groups were statistically significant on the fourth and fifth days after the end of exposure (P < 0.05); the control group showed lower values than the aluminum group, and the wild type C57BL/6 mice showed lower values than the ApoE4 transgenic type mice; however, the interaction between genotype and aluminum was not statistically significant (P>0.05). The frequencies of crossing the platform in the C57BL/6 control group, the C57BL/6 aluminum group, the ApoE4 control group, and the ApoE4 aluminum group were (2.86±0.99), (1.88±0.64), (2.63±0.77), and (0.50±0.53), respectively; the interaction between genotype and aluminum was statistically significant (P < 0.05). The densities of dendritic spines in the C57BL/6 control group and aluminum group as well as the ApoE4 control group and aluminum group were (0.57±0.06), (0.34±0.05), (0.39±0.05), and (0.26±0.04) spines per μm, respectively; the interaction between genotype and aluminum was statistically significant (P < 0.05). Western blotting results showed that aluminum and ApoE4 gene had interactions with ApoER2 and LRP1 protein expressions (P < 0.05), and both aluminum exposure and ApoE4 genotype led to decreased expression levels of ApoER2 and LRP1 proteins, but had no interaction with APP or VLDLRs protein expressions (P < 0.05). The results of Elisa showed that there was an interaction between aluminum and ApoE4 gene in Aβ42 protein (P < 0.05), but not in Aβ40 (P>0.05).

Conclusion Aluminum and ApoE4 gene interact with each other on learning and memory in mice, especially on spatial learning and memory ability. The interaction between aluminum and ApoE4 gene on synaptic plasticity in hippocampal CA1 region indicates that the combined action may have an effect on synaptic plasticity. The interaction between aluminum and ApoE4 gene on Aβ content, especially on Aβ42 content, may be related to the decrease in ApoER2 and LRP1 of the low density lipoprotein family.