Modulation of secreted beta-amyloid precursor protein and amyloid beta-peptide in brain by cholesterol.

The Journal of Biological Chemistry
D S HowlandD G Flood

Abstract

The effects of dietary cholesterol on brain amyloid precursor protein (APP) processing were examined using an APP gene-targeted mouse, genetically humanized in the amyloid beta-peptide (Abeta) domain and expressing the Swedish familial Alzheimer's disease mutations. These mice express endogenous levels of APP holoprotein and abundant human Abeta. Increased dietary cholesterol led to significant reductions in brain levels of secreted APP derivatives, including sAPPalpha, sAPPbeta, Abeta1-40, and Abeta1-42, while having little to no effect on cell-associated species, including full-length APP and the COOH-terminal APP processing derivatives. The changes in levels of sAPP and Abeta in brain all were negatively correlated with serum cholesterol levels and levels of serum and brain apoE. These results demonstrate that secreted APP processing derivatives and Abeta can be modulated in the brain of an animal by diet and provide evidence that cholesterol plays a role in the modulation of APP processing in vivo. APP gene-targeted mice lacking apoE, also have high serum cholesterol levels but do not show alterations in APP processing, suggesting that effects of cholesterol on APP processing require the presence of apoE.

References

Mar 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·G L CaporasoP Greengard
May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·J A PiedrahitaN Maeda
Oct 1, 1991·Biochimie·P L Yeagle
Nov 1, 1990·Neurobiology of Aging·D L SparksW R Markesbery
Apr 4, 1986·Science·M S Brown, J L Goldstein
Sep 1, 1986·The Journal of Clinical Investigation·R E GreggH B Brewer
May 1, 1985·Journal of Neurochemistry·Y Sakakihara, J J Volpe
Jan 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·L OrciP Vassalli
Oct 24, 1995·Proceedings of the National Academy of Sciences of the United States of America·M MurataK Simons
Dec 1, 1995·Experimental Neurology·E MasliahA D Roses
Jan 1, 1995·Molecular Membrane Biology·F SchroederC Joiner
Dec 1, 1994·The Journal of Cell Biology·E J SmartR G Anderson
Dec 6, 1994·Proceedings of the National Academy of Sciences of the United States of America·M CitronD J Selkoe
Sep 18, 1993·Lancet·J PoirierS Gauthier
Sep 3, 1993·Science·M S Bretscher, S Munro
Jan 1, 1993·Annual Review of Nutrition·D K SpadyJ M Dietschy
Mar 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·W J StrittmatterA D Roses

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Citations

Oct 31, 2002·Human Psychopharmacology·Kurt Heininger
Aug 11, 2000·Microscopy Research and Technique·D L SparksJ C Hunsaker
Dec 10, 2003·Current Atherosclerosis Reports·Paolo Calabro, Edward T H Yeh
Dec 17, 2008·Current Neurology and Neuroscience Reports·Steven A Greenberg
Sep 6, 2002·Journal of Molecular Neuroscience : MN·Suzana S PetanceskaLorenzo M Refolo
Nov 16, 2012·Journal of Biosciences·V KaliyamurthiG Victor Rajamanickam
Dec 21, 2010·Journal of Applied Genetics·Ivan A Borbon, Robert P Erickson
Apr 6, 2004·Mechanisms of Ageing and Development·Wei-Yi OngBarry Halliwell
Apr 15, 2004·Medical Hypotheses·Samuel T Henderson
Apr 20, 2004·Toxicology Letters·Naoki KiyosawaNaochika Matsunuma
Jun 11, 2002·Journal of Molecular Biology·Christopher M YipJoAnne McLaurin
Feb 8, 2003·Brain Research. Molecular Brain Research·Mark P BurnsKaren Duff
Apr 13, 2000·Neurochemistry International·H KölschM L Rao
Oct 24, 2002·Neurobiology of Aging·W Gibson WoodSvetlana V Chochina
Feb 26, 2003·Neurobiology of Aging·M Axel WollmerAndreas Papassotiropoulos
Jul 30, 2003·Neurobiology of Aging·In-Ho ParkInhee Mook-Jung
Jul 30, 2003·Neurobiology of Aging·Barbara BorroniAlessandro Padovani
Jan 25, 2003·Experimental Gerontology·Marco Racchi, Stefano Govoni
Jul 11, 2002·Free Radical Biology & Medicine·Miguel A PappollaLorenzo M Refolo
Aug 17, 1999·Current Opinion in Cell Biology·T V Kurzchalia, R G Parton
Oct 9, 2001·Drug Discovery Today·T E. Golde, C B. Eckman
Jul 18, 2008·The British Journal of Nutrition·Menuka M Pallebage-GamarallageJohn C L Mamo
Nov 10, 2011·The Proceedings of the Nutrition Society·Martha C Morris
Feb 4, 1999·Journal of Neurochemistry·J Mills, P B Reiner
Aug 2, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yan ZhouKumar Sambamurti
Sep 10, 2002·Alzheimer Disease and Associated Disorders·Milita CrisbyBengt Winblad
Mar 27, 2001·Current Opinion in Lipidology·J M Dietschy, S D Turley
May 10, 2006·Genes, Brain, and Behavior·M GrazinaC Oliveira
Dec 14, 2002·Annals of the New York Academy of Sciences·Mark Burns, Karen Duff
Nov 18, 2005·Journal of Neurology, Neurosurgery, and Psychiatry·I MasseF Pasquier
Nov 18, 2003·Journal of Neurology, Neurosurgery, and Psychiatry·V W HendersonL Dennerstein
Mar 10, 2001·Reviews in the Neurosciences·P K Panegyres

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