title: An in vitro and in vivo study of early deficits in associative learning in transgenic mice that over-express a mutant form of human APP associated with Alzheimer's disease.
abstract: Transgenic mice over-expressing a mutated form of the human amyloid precursor protein (APP, 695 isoform) bearing a mutation associated with Alzheimer's disease (V642I, so-called London mutation, hereafter APPLd2) and wild-type controls were studied at age periods (3 and 10 months) prior to the overt development of neuritic amyloid plaques. Both 3- and 10-month-old APPLd2 mice had reflex eyelid responses like those of controls, but only younger mice were able to acquire a classical conditioning of eyelid responses in a trace paradigm. In vitro studies on hippocampal slices showed that 10-month-old APPLd2 mice also presented deficits in paired-pulse facilitation and long-term potentiation, but presented a normal synaptic activation of CA1 pyramidal cells by the stimulation of Schaffer collaterals. It is proposed that definite functional changes may appear well in advance of noticeable structural alterations in this animal model of Alzheimer's disease, and that specific learning tasks could have a relevant diagnostic value.
authors.affiliation: División de Neurociencias, Universidad Pablo de Olavide, 41013-Sevilla, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Domínguez-del-Toro
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez-Moreno
authors.forename: Elena
authors.initials: E
authors.lastname: Porras-García
authors.forename: Raudel
authors.initials: R
authors.lastname: Sánchez-Campusano
authors.forename: Véronique
authors.initials: V
authors.lastname: Blanchard
authors.forename: Michel
authors.initials: M
authors.lastname: Laville
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhme
authors.forename: Jesús
authors.initials: J
authors.lastname: Benavides
authors.forename: José M
authors.initials: JM
authors.lastname: Delgado-García
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology; D004195:Disease Models, Animal; D005071:Evoked Potentials; D005143:Eyelids / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D011930:Reaction Time
chemical_list: D016564:Amyloid beta-Protein Precursor