Amyloid precursor protein increases cortical neuron size in transgenic mice☆
Received 18 October 2007; received in revised form 13 December 2007; accepted 28 December 2007. published online 28 February 2008.
Abstract
The amyloid precursor protein (APP) is the source of β-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 (μm3) 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.
aDepartment of Medicine, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
bDepartment of Pathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
cDepartment of Neurology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
dDepartment of Neuroscience, University of Florida, 100 Newell Drive, Gainesville, FL 32610, USA
Corresponding author at: Department of Pathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA. Tel.: +410 955 5165; fax: +410 955 9777.
☆ All procedures were conducted according to NIH guide for animal care and approved by the JHU Institutional Animal Care and Use Committee.
ABSTRACT