title: Amyloid precursor protein increases cortical neuron size in transgenic mice.
abstract: The amyloid precursor protein (APP) is the source of beta-amyloid, a pivotal peptide in the pathogenesis of Alzheimer's disease (AD). This study examines the possible effect of APP transgene expression on neuronal size by measuring the volumes of cortical neurons (microm(3)) in transgenic mouse models with familial AD Swedish mutation (APPswe), with or without mutated presenilin1 (PS1dE9), as well as in mice carrying wild-type APP (APPwt). Overexpression of APPswe and APPwt protein, but not of PS1dE9 alone, resulted in a greater percentage of medium-sized neurons and a proportionate decrease in the percentage of small-sized neurons. Our observations indicate that the overexpression of mutant (APPswe) or wild-type APP in transgenic mice is necessary and sufficient for hypertrophy of cortical neurons. This is highly suggestive of a neurotrophic effect and also raises the possibility that the lack of neuronal loss in transgenic mouse models of AD may be attributed to overexpression of APP.
authors.affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, 558 Ross Research Building, Baltimore, MD 21205, USA.
authors.forename: Esther S
authors.initials: ES
authors.lastname: Oh
authors.forename: Alena V
authors.initials: AV
authors.lastname: Savonenko
authors.forename: Julie F
authors.initials: JF
authors.lastname: King
authors.forename: Stina M
authors.initials: SM
authors.lastname: Fangmark Tucker
authors.forename: Gay L
authors.initials: GL
authors.lastname: Rudow
authors.forename: Guilian
authors.initials: G
authors.lastname: Xu
authors.forename: David R
authors.initials: DR
authors.lastname: Borchelt
authors.forename: Juan C
authors.initials: JC
authors.lastname: Troncoso
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D048429:Cell Size; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012727:Sex Characteristics
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D058255:Protease Nexins; D011956:Receptors, Cell Surface