Amyloid precursor protein increases cortical neuron size in transgenic mice

Oh, Esther S.; Savonenko, Alena V.; King, Julie F.; Fangmark Tucker, Stina M.; Rudow, Gay L.; Xu, Guilian; Borchelt, David R.; Troncoso, Juan C.

doi:10.1016/j.neurobiolaging.2007.12.024

« Previous Next »Neurobiology of Aging
Volume 30, Issue 8 , Pages 1238-1244, August 2009

Amyloid precursor protein increases cortical neuron size in transgenic mice☆

Esther S. Oh
- Department of Medicine, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
- Department of Pathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
Alena V. Savonenko
- Department of Pathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
Julie F. King
- Department of Medicine, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
Stina M. Fangmark Tucker
- Department of Pathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
Gay L. Rudow
- Department of Pathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
Guilian Xu
- Department of Neuroscience, University of Florida, 100 Newell Drive, Gainesville, FL 32610, USA
David R. Borchelt
- Department of Neuroscience, University of Florida, 100 Newell Drive, Gainesville, FL 32610, USA
Juan C. Troncoso
- Department of Pathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
- Department of Neurology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, 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.

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.

Keywords: Neuron size, Transgenic mouse models of Alzheimer's disease, Stereology, Amyloid precursor protein