Independent effects of APOE on cholesterol metabolism and brain Abeta levels in an Alzheimer disease mouse model

Human Molecular Genetics
Karen MannBruce Lamb

Abstract

The APOE epsilon4 allele is the most significant genetic risk factor associated with Alzheimer's disease to date. Epidemiological studies have demonstrated that inheritance of one or more epsilon4 alleles affects both the age of onset and the severity of pathology development. Dosage of APOE epsilon2 and epsilon3 alleles, however, appear to be protective against the effects of epsilon4. Although much of the biology of APOE in peripheral cholesterol metabolism is understood, its role in brain cholesterol metabolism and its impact on AD development is less defined. Several APOE transgenic models have been generated to study the effects of APOE alleles on APP processing and Abeta pathology. However, these models have potential limitations that confound our understanding of the effects of apolipoprotein E (APOE) levels and cholesterol metabolism on disease development. To circumvent these limitations, we have taken a genomic-based approach to better understand the relationship between APOE alleles, cholesterol and Abeta metabolism. We have characterized APOE knock-in mice, which express each human allele under the endogenous regulatory elements, on a defined C57BL6/J background. These mice have significantly different serum cholest...Continue Reading

Citations

Sep 10, 2005·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Amy C LossieMonica J Justice
Apr 7, 2012·International Journal of Alzheimer's Disease·Ramón CacabelosMasatoshi Takeda
Jan 4, 2006·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·Tara L Spires, Bradley T Hyman
Mar 31, 2005·Seminars in Cell & Developmental Biology·Jean E VanceBarbara Karten
Sep 24, 2005·Bipolar Disorders·Clare L BeasleyThomas A Bayer
Jun 18, 2005·Journal of Nursing Scholarship : an Official Publication of Sigma Theta Tau International Honor Society of Nursing·Suzanne FeethamAda Sue Hinshaw
Aug 15, 2009·Neuron·Jungsu KimDavid M Holtzman
Dec 24, 2017·Molecular Neurodegeneration·Joanna L Jankowsky, Hui Zheng
Oct 2, 2012·American Journal of Medical Genetics. Part a·Rao FuForbes D Porter
Feb 26, 2019·Current Protocols in Pharmacology·Kevin Mullane, Michael Williams
Sep 9, 2018·Nature Reviews. Neuroscience·Jürgen GötzMichel Goedert
May 6, 2020·Molecular Brain·Wenchen ZhaoCheryl L Wellington
Jul 22, 2019·Trends in Pharmacological Sciences·Manish D ParanjpeMarina Sirota
Mar 17, 2007·Progress in Neuro-psychopharmacology & Biological Psychiatry·Carmen Diaz-SastreJose de Leon

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