Alterations in Brain Cholesterol Metabolism in the APPSLxPS1mut mouse, a Model for Alzheimer's Disease
作者： Tim Vanmierlo , Vincent W. Bloks , Leonie C. van Vark-van der Zee , Kris Rutten , Anja Kerksiek
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摘要: Disturbances in cerebral cholesterol metabolism have been implicated the pathogenesis of Alzheimer's disease (AD). Here, we provide evidence that alterations brain homeostasis also can be a consequence progression. We found APPSLxPS1mut mice, at age 9 months when AD-like pathology starts to develop, display increased levels precursor desmosterol and metabolite 27-hydroxy(OH)cholesterol their cerebellum comparison with wild-type controls. At 21 months, contains abundant amyloid deposits, had further (> 200% mice) all regions examined. 24(S)-OHcholesterol were hippocampus while 27-OHcholesterol exclusively. Brain remained unaffected. In line fact are Liver X Receptor (LXR) activators, LXR-target genes Abca1 Apoc1 upregulated predominantly mice both ages evaluated. The reduced expression enzyme converts into cholesterol, Selective AD indicator 1 gene (Seladin-1/Dhcr24), cortex may underlie month-old mice.
narcis.nl参考文章(42)
Henri J. Huttunen, Luigi Puglielli, Blake C. Ellis, Laura A. MacKenzie Ingano, Dora M. Kovacs, Novel N-terminal Cleavage of APP Precludes Aβ Generation in ACAT-Defective AC29 Cells Journal of Molecular Neuroscience. ,vol. 37, pp. 6- 15 ,(2009) , 10.1007/S12031-008-9088-0
Dieter Lütjohann, Andreas Brzezinka, Esther Barth, Dorothee Abramowski, Matthias Staufenbiel, Klaus von Bergmann, Konrad Beyreuther, Gerd Multhaup, Thomas A. Bayer, Profile of cholesterol-related sterols in aged amyloid precursor protein transgenic mouse brain. Journal of Lipid Research. ,vol. 43, pp. 1078- 1085 ,(2002) , 10.1194/JLR.M200071-JLR200
Jian-Sheng Gong, Naoya Sawamura, Kun Zou, Juro Sakai, Katsuhiko Yanagisawa, Makoto Michikawa, Amyloid β‐protein affects cholesterol metabolism in cultured neurons: Implications for pivotal role of cholesterol in the amyloid cascade Journal of Neuroscience Research. ,vol. 70, pp. 438- 446 ,(2002) , 10.1002/JNR.10347
Steve Pedrini, Troy L Carter, George Prendergast, Suzana Petanceska, Michelle E Ehrlich, Sam Gandy, Modulation of Statin-Activated Shedding of Alzheimer APP Ectodomain by ROCK PLOS Medicine. ,vol. 2, ,(2005) , 10.1371/JOURNAL.PMED.0020018
K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, G. Cole, Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice Science. ,vol. 274, pp. 99- 102 ,(1996) , 10.1126/SCIENCE.274.5284.99
Erik G. Lund, Chonglun Xie, Tiina Kotti, Stephen D. Turley, John M. Dietschy, David W. Russell, Knockout of the Cholesterol 24-Hydroxylase Gene in Mice Reveals a Brain-specific Mechanism of Cholesterol Turnover Journal of Biological Chemistry. ,vol. 278, pp. 22980- 22988 ,(2003) , 10.1074/JBC.M303415200
Huaqi Xiong, Debbie Callaghan, Aimee Jones, Douglas G. Walker, Lih-Fen Lue, Thomas G. Beach, Lucia I. Sue, John Woulfe, Huaxi Xu, Danica B. Stanimirovic, Wandong Zhang, Cholesterol retention in Alzheimer's brain is responsible for high β-and γ-secretase activities and Aβ production Neurobiology of Disease. ,vol. 29, pp. 422- 437 ,(2008) , 10.1016/J.NBD.2007.10.005
Karen Duff, Chris Eckman, Cindy Zehr, Xin Yu, Cristian-Mihail Prada, Jordi Perez-tur, Mike Hutton, Luc Buee, Yasuo Harigaya, Debra Yager, David Morgan, Marcia N. Gordon, Leigh Holcomb, Lawrence Refolo, Brenda Zenk, John Hardy, Steven Younkin, Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1 Nature. ,vol. 383, pp. 710- 713 ,(1996) , 10.1038/383710A0
Allison B. Reiss, Cholesterol and apolipoprotein E in Alzheimer's disease American Journal of Alzheimers Disease and Other Dementias. ,vol. 20, pp. 91- 96 ,(2005) , 10.1177/153331750502000208
Feng-Shiun Shie, Lee-Way Jin, David G. Cook, James B. Leverenz, Renée C. LeBoeuf, Diet-induced hypercholesterolemia enhances brain Aβ accumulation in transgenic mice Neuroreport. ,vol. 13, pp. 455- 459 ,(2002) , 10.1097/00001756-200203250-00019