Use of in Vivo Models to Study the Role of Cholesterol in the Etiology of Alzheimer's Disease

Overview

Journal Neurochem Res

Specialties Chemistry
Neurology

Date 2003 May 10

PMID 12737522

Citations 5

Authors

Mark Burns

Karen Duff

Affiliations

Soon will be listed here.

Abstract

Cholesterol has been implicated in the pathogenesis of Alzheimer's disease, both through intracellular effects, and through an extracellular effect due to its physical interaction with plaque associated amyloid. Epidemiology studies have implicated high cholesterol as a risk factor for AD, and have shown that the use of cholesterol reducing agents (statins) can be protective against the disease. We, and others have shown that cholesterol levels modulate the processing of the amyloid precursor protein (APP) both in vivo and in vitro, affecting the accumulation of Abeta (Abeta) peptides which may directly impact the risk of AD. This review describes the biology of sterols, and identifies how cholesterol may exacerbate the pathogenesis of AD. Data from in vivo and in vitro studies will then be presented to describe how treatments aimed at modulating lipid levels may be efficacious in treating AD.

Citing Articles

USE OF FUSED CIRCULATIONS TO INVESTIGATE THE ROLE OF APOLIPOPROTEIN E AS AMYLOID CATALYST AND PERIPHERAL SINK IN ALZHEIMER'S DISEASE.

Nilsson L, Gografe S, Costa D, Hughes T, Dressler D, Potter H Technol Innov. 2013; 14(2):199-208.

PMID: 23626867 PMC: 3635498. DOI: 10.3727/194982412X13462021398010.

ABCA1 polymorphisms and Alzheimer's disease.

Wavrant-De Vrieze F, Compton D, Womick M, Arepalli S, Adighibe O, Li L Neurosci Lett. 2007; 416(2):180-3.

PMID: 17324514 PMC: 1945126. DOI: 10.1016/j.neulet.2007.02.010.

Alzheimer's disease and cholesterol: the fat connection.

Canevari L, Clark J Neurochem Res. 2006; 32(4-5):739-50.

PMID: 17191138 DOI: 10.1007/s11064-006-9200-1.

Prevention of Alzheimer disease. Encouraging evidence.

Scalco M, van Reekum R Can Fam Physician. 2006; 52:200-7.

PMID: 16529393 PMC: 1479722.

Characterisation of cerivastatin as a P-glycoprotein substrate: studies in P-glycoprotein-expressing cell monolayers and mdr1a/b knock-out mice.

Kivisto K, Zukunft J, Hofmann U, Niemi M, Rekersbrink S, Schneider S Naunyn Schmiedebergs Arch Pharmacol. 2004; 370(2):124-30.

PMID: 15322734 DOI: 10.1007/s00210-004-0948-z.

References

Wang X, Sato R, Brown M, Hua X, Goldstein J . SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell. 1994; 77(1):53-62. DOI: 10.1016/0092-8674(94)90234-8. View

Hutton M, Perez-Tur J, Hardy J . Genetics of Alzheimer's disease. Essays Biochem. 1999; 33:117-31. DOI: 10.1042/bse0330117. View

Jost P, Griffith O, Capaldi R, Vanderkooi G . Evidence for boundary lipid in membranes. Proc Natl Acad Sci U S A. 1973; 70(2):480-4. PMC: 433287. DOI: 10.1073/pnas.70.2.480. View

Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C . Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature. 1995; 373(6514):523-7. DOI: 10.1038/373523a0. View

Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S . Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science. 1996; 274(5284):99-102. DOI: 10.1126/science.274.5284.99. View

Jick H, Zornberg G, Jick S, Seshadri S, Drachman D . Statins and the risk of dementia. Lancet. 2000; 356(9242):1627-31. DOI: 10.1016/s0140-6736(00)03155-x. View

Refolo L, Malester B, Lafrancois J, Wang R, Tint G, Sambamurti K . Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiol Dis. 2000; 7(4):321-31. DOI: 10.1006/nbdi.2000.0304. View

Holcomb L, Gordon M, McGowan E, Yu X, Benkovic S, Jantzen P . Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat Med. 1998; 4(1):97-100. DOI: 10.1038/nm0198-097. View

Bales K, Verina T, Dodel R, Du Y, Altstiel L, Bender M . Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition. Nat Genet. 1997; 17(3):263-4. DOI: 10.1038/ng1197-263. View

10.

Yamazaki T, Chang T, Haass C, Ihara Y . Accumulation and aggregation of amyloid beta-protein in late endosomes of Niemann-pick type C cells. J Biol Chem. 2000; 276(6):4454-60. DOI: 10.1074/jbc.M009598200. View

11.

Bodovitz S, Klein W . Cholesterol modulates alpha-secretase cleavage of amyloid precursor protein. J Biol Chem. 1996; 271(8):4436-40. DOI: 10.1074/jbc.271.8.4436. View

12.

Launer L, White L, Petrovitch H, Ross G, Curb J . Cholesterol and neuropathologic markers of AD: a population-based autopsy study. Neurology. 2001; 57(8):1447-52. DOI: 10.1212/wnl.57.8.1447. View

13.

Jost P, Griffith O . Lipid-lipid and lipid-protein interactions in membranes. Pharmacol Biochem Behav. 1980; 13 Suppl 1:155-65. DOI: 10.1016/s0091-3057(80)80025-6. View

14.

Duff K, Eckman C, Zehr C, Yu X, Prada C, Perez-Tur J . Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature. 1996; 383(6602):710-3. DOI: 10.1038/383710a0. View

15.

Puglielli L, Konopka G, Ingano L, Berezovska O, Hyman B, Chang T . Acyl-coenzyme A: cholesterol acyltransferase modulates the generation of the amyloid beta-peptide. Nat Cell Biol. 2001; 3(10):905-12. DOI: 10.1038/ncb1001-905. View

16.

Refolo L, Pappolla M, Lafrancois J, Malester B, Schmidt S, Tint G . A cholesterol-lowering drug reduces beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease. Neurobiol Dis. 2001; 8(5):890-9. DOI: 10.1006/nbdi.2001.0422. View

17.

Notkola I, Sulkava R, Pekkanen J, Erkinjuntti T, Ehnholm C, Kivinen P . Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease. Neuroepidemiology. 1998; 17(1):14-20. DOI: 10.1159/000026149. View

18.

Petanceska S, DeRosa S, Olm V, Diaz N, Sharma A, Duff K . Statin therapy for Alzheimer's disease: will it work?. J Mol Neurosci. 2002; 19(1-2):155-61. DOI: 10.1007/s12031-002-0026-2. View

19.

Howland D, Trusko S, Savage M, Reaume A, Lang D, Hirsch J . Modulation of secreted beta-amyloid precursor protein and amyloid beta-peptide in brain by cholesterol. J Biol Chem. 1998; 273(26):16576-82. DOI: 10.1074/jbc.273.26.16576. View

20.

Fra A, Williamson E, Simons K, Parton R . Detergent-insoluble glycolipid microdomains in lymphocytes in the absence of caveolae. J Biol Chem. 1994; 269(49):30745-8. View