Dataset Information

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.

SUBMITTER: Oh ES

PROVIDER: S-EPMC2796369 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Amyloid precursor protein increases cortical neuron size in transgenic mice.

Oh Esther S ES Savonenko Alena V AV King Julie F JF Fangmark Tucker Stina M SM Rudow Gay L GL Xu Guilian G Borchelt David R DR Troncoso Juan C JC

Neurobiology of aging 20080304 8

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 P ...[more]

PMID: 18304698

Similar Datasets

Project description:Although the important role of amyloid precursor protein (APP) in vascular diseases associated with Alzheimer's disease (AD) has been demonstrated, the underlying molecular mechanisms and physiological consequences are unclear. We aimed to evaluate vascular inflammation and atherosclerosis in Swedish mutant of human APP transgenic (APPsw-Tg) and ApoE-/-/APPsw-Tg mice. We also aimed to explore the mechanisms underlying any changes observed in these mice compared with non-Tg controls. Methods: The transgenic and non-Tg mouse strains were subjected to partial ligation of the left carotid artery to induce atherosclerotic changes, which were measured using histological approaches, immunohistochemistry, quantitative polymerase chain reaction, and gene expression microarrays. Results: Our results showed increased vascular inflammation, arterial wall thickness, and atherosclerosis in APPsw-Tg and ApoE-/-/APPsw-Tg mice. We further found that the expression of chitinase-3-like-1 (Chi3l1) is increased in the APPsw-Tg mouse artery and Chi3l1 mediates endothelial cell (EC) inflammation and vascular smooth muscle cell (VSMC) activation, which in turn exacerbates atherosclerosis. In addition, using two publicly available microarray datasets from the dorsolateral prefrontal cortex of people with AD and unaffected controls as well as inflamed human umbilical vein endothelial cells, we found that Chi3l1 and associated inflammatory gene were significantly associated with AD, evaluated by co-expression network analysis and functional annotation. Knockdown of Chi3l1 in the arterial endothelium in vivo suppressed the development of atherosclerosis. We also show that microRNA 342-3p (miR-342-3p) inhibits EC inflammation and VSMC activation through directly targeting Chi3l1, and that APPsw increased Chi3l1 expression by reducing miR-342-3p expression in the arterial endothelium, promoting atherosclerosis. Conclusion: Our findings suggest that targeting Chi3l1 might provide new diagnostic and therapeutic strategies for vascular diseases in patients with AD.

Dataset Information

Amyloid precursor protein increases cortical neuron size in transgenic mice.

Publications

Amyloid precursor protein increases cortical neuron size in transgenic mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure