Amyloid precursor protein increases cortical neuron size in transgenic mice

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• 作者：Esther S. Oh ; Alena V. Savonenko ; Julie F. King ; Stina M. Fangmark Tucker ; Gay L. Rudow ; Guilian Xu ; David R. Borchelt ; Juan C. Troncoso
• 关键词：Neuron size ; Transgenic mouse models of Alzheimer's disease ; Stereology ; Amyloid precursor protein
• 刊名：Neurobiology of Aging
• 出版年：2009
• 出版时间：August 2009
• 年：2009
• 卷：30
• 期：8
• 页码：1238-1244
• 全文大小：180 K

文摘

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.