title: ApoE isoform affects LTP in human targeted replacement mice.
abstract: 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.
authors.affiliation: Department of Pediatrics, Alzheimer's Disease Core Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60614, USA. btrommer@northwestern.edu
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Trommer
authors.forename: Chirag
authors.initials: C
authors.lastname: Shah
authors.forename: Sung Hwan
authors.initials: SH
authors.lastname: Yun
authors.forename: Georgi
authors.initials: G
authors.lastname: Gamkrelidze
authors.forename: Emily S
authors.initials: ES
authors.lastname: Pasternak
authors.forename: Gui Lan
authors.initials: GL
authors.lastname: Ye
authors.forename: Michelle
authors.initials: M
authors.lastname: Sotak
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Sullivan
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Pasternak
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: LaDu
mesh_terms: 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*
chemical_list: D001057:Apolipoproteins E; D020033:Protein Isoforms