Hypercholesterolemia and neurodegeneration. Comparison of hippocampal phenotypes in LDLr knockout and APPswe/PS1dE9 mice

Experimental Gerontology
Miren EttchetoAntoni Camins

Abstract

Previous studies suggest that Alzheimer's disease (AD) neurobiology could not be explained solely by an increase in β-amyloid levels. Recently, it has been proposed that alterations in brain cholesterol metabolism may contribute to the pathogenesis of AD. In the present work, we focus on early changes in the hippocampal phenotypes of two mouse models in which cognitive impairments were previously described: a) the hypercholesterolemic LDL receptor knockout (LDLr -/-) and b) the APPswe/PS1dE9 (APP/PS1) transgenic model of familial AD. Our initial analysis, subsequent validation and additional experiments at the mRNA and protein levels demonstrate some parallels between the hippocampal phenotypes of these 2 mouse models, however our data suggest that the molecular mechanisms leading to cognitive decline are distinct in LDLr -/- and APP/PS1 animals. Genes related to cytokine signaling were significantly down-regulated in LDLr -/- mice when compared to both the wild-type and APP/PS1 mice, and these include prostaglandin-endoperoxide synthases 1 and 2 (ptgs1 and 2) and nerve grow factor (ngf). We have also detected reduced expression of genes related to lipid metabolism in LDLr -/- mice: peroxisome proliferator activated receptor ga...Continue Reading

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Citations

Dec 8, 2015·Journal of Nutritional Science and Vitaminology·Koji FukuiShiro Urano
Dec 18, 2016·Nanomedicine : Nanotechnology, Biology, and Medicine·Elena Sánchez-LópezMaria Luisa García
Mar 17, 2017·Frontiers in Molecular Neuroscience·Theresa PohlkampJoachim Herz
Dec 10, 2019·Journal of Alzheimer's Disease : JAD·Jade de OliveiraAndreza F de Bem
Jun 15, 2021·Pharmacological Reports : PR·Karolina MaciejewskaPaweł Szymański

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