ApoE isoform affects LTP in human targeted replacement mice

Inheritance of the &egr;4 allele for apolipoprotein E (apoE) increases the risk of Alzheimer disease and memory impairment, whereas &egr;2 decreases these risks compared with the most common &egr;3 allele, but the mechanism for these effects is unknown. Long-term potentiation (LTP) is an experimentally induced increase in synaptic efficacy that models memory. Using hippocampal slices from wild type (WT), apoE knockout (apoE-KO), and targeted replacement mice expressing human apoE2, E3, or E4 (apoE-TR) we found that although all strains had comparable basal synaptic transmission, LTP was significantly greater in WT and apoE3-TR than in apoE-KO, apoE2-TR or apoE4-TR. This novel system may be used to investigate the mechanisms of apoE isoform dependent modulation of susceptibility to memory impairment.

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