ApoE isoform affects LTP in human targeted replacement mice

Neuroreport. 2004 Dec 3;15(17):2655-8. doi: 10.1097/00001756-200412030-00020.


Inheritance of the epsilon4 allele for apolipoprotein E (apoE) increases the risk of Alzheimer disease and memory impairment, whereas epsilon2 decreases these risks compared with the most common epsilon3 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism*
  • Electric Stimulation / methods
  • Hippocampus / physiology*
  • Hippocampus / radiation effects
  • Humans
  • In Vitro Techniques
  • Long-Term Potentiation / physiology*
  • Long-Term Potentiation / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*


  • Apolipoproteins E
  • Protein Isoforms