ApoE isoform affects LTP in human targeted replacement mice.
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.
Trommer
Barbara L
BL
Department of Pediatrics, Alzheimer's Disease Core Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60614, USA. btrommer@northwestern.edu
Shah
Chirag
C
Yun
Sung Hwan
SH
Gamkrelidze
Georgi
G
Pasternak
Emily S
ES
Ye
Gui Lan
GL
Sotak
Michelle
M
Sullivan
Patrick M
PM
Pasternak
Joseph F
JF
LaDu
Mary Jo
MJ
D000704:Analysis of Variance; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D004558:Electric Stimulation / Q000379:methods; D006624:Hippocampus / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology* / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*
D001057:Apolipoproteins E; D020033:Protein Isoforms