CYP46A1 inhibition, brain cholesterol accumulation and neurodegeneration pave the way for Alzheimer's disease

Brain

Volumn 138, Issue 8, 2015, Pages 2383-2398

  Djelti, Fathia ^a   Braudeau, Jerome ^a   Hudry, Eloise ^a   Dhenain, Marc ^b   Varin, Jennifer ^c   Bièche, Ivan ^c   Marquer, Catherine ^d   Chali, Farah ^d   Ayciriex, Sophie ^c   Auzeil, Nicolas ^c   Alves, Sandro ^a   Langui, Dominique ^d   Potier, Marie Claude ^d   Laprevote, Olivier ^c   Vidaud, Michel ^c   Duyckaerts, Charles ^d   Miles, Richard ^d   Aubourg, Patrick ^a   Cartier, Nathalie ^a  

^a Bicetre Hospital   (France)

^b INSTITUT DE RADIOPROTECTION ET DE SÛRETÉ NUCLÉAIRE   (France)

^c UNIVERSITÉ PARIS DESCARTES   (France)

^d SORBONNE UNIVERSITÉ   (France)

Author keywords

24S hydroxycholesterol; Alzheimer's disease; cholesterol; Cyp46a1; neurodegeneration

Indexed keywords

AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; AMYLOID PRECURSOR PROTEIN; CHOLESTEROL; CHOLESTEROL 24 HYDROXYLASE; CYTOCHROME P450 REDUCTASE; MESSENGER RNA; PARVOVIRUS VECTOR; SHORT HAIRPIN RNA; TAU PROTEIN; UNCLASSIFIED DRUG; AMYLOID BETA PROTEIN; CHOLESTEROL 24-HYDROXYLASE; ENZYME INHIBITOR; STEROID MONOOXYGENASE;

ALZHEIMER DISEASE; AMYLOID PLAQUE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; BRAIN ATROPHY; CARBOXY TERMINAL SEQUENCE; CHOLESTEROL TRANSPORT; COGNITIVE DEFECT; CONTROLLED STUDY; DISEASE EXACERBATION; ENDOPLASMIC RETICULUM STRESS; ENZYME INHIBITION; EXPLORATORY BEHAVIOR; FEMALE; GENE EXPRESSION; HIPPOCAMPAL CA1 REGION; HIPPOCAMPAL CA3 REGION; HOMEOSTASIS; LIPID RAFT; LIPID STORAGE; METHODOLOGY; MOUSE; MOUSE MODEL; NERVE CELL NECROSIS; NERVE DEGENERATION; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN METABOLISM; PROTEIN PHOSPHORYLATION; PYRAMIDAL NERVE CELL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA INTERFERENCE; WESTERN BLOTTING; ANIMAL; ANTAGONISTS AND INHIBITORS; BRAIN; C57BL MOUSE; METABOLISM; NERVE CELL; PHYSIOLOGY; TRANSGENIC MOUSE;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; BRAIN; CHOLESTEROL; ENZYME INHIBITORS; FEMALE; HOMEOSTASIS; MICE, INBRED C57BL; MICE, TRANSGENIC; NEURONS; STEROID HYDROXYLASES;

EID: 84940093906     PISSN: 00068950     EISSN: 14602156     Source Type: Journal    
DOI: 10.1093/brain/awv166     Document Type: Article

References (61)

1. Ando K, Leroy K, Heraud C, Yilmaz Z, Authelet M, Suain V, et al. Accelerated human mutant tau aggregation by knocking out murine tau in a transgenic mouse model. Am J Pathol 2011; 178: 803-16.
2. Asselah T, Bieche I, Mansouri A, Laurendeau I, Cazals-Hatem D, Feldmann G, et al. In vivo hepatic endoplasmic reticulum stress in patients with chronic hepatitis C. J Pathol 2010; 221: 264-74.
3. Ayciriex S, Regazzetti A, Gaudin M, Prost E, Dargere D, Massicot F, et al. Development of a novel method for quantification of sterols and oxysterols by UPLC-ESI-HRMS: application to a neuroinflammation rat model. Anal Bioanal Chem 2012; 404: 3049-59.
4. Bauer M, Kinkl N, Meixner A, Kremmer E, Riemenschneider M, Forstl H, et al. Prevention of interferon-stimulated gene expression using microRNA-designed hairpins. Gene Ther 2009; 16: 142-7.
5. Bieche I, Lerebours F, Tozlu S, Espie M, Marty M, Lidereau R. Molecular profiling of inflammatory breast cancer: identification of a poor-prognosis gene expression signature. Clin Cancer Res 2004; 10: 6789-95.
6. Bjorkhem I. Crossing the barrier: oxysterols as cholesterol transporters and metabolic modulators in the brain. J Intern Med 2006; 260: 493-508.
7. Bjorkhem I, Lutjohann D, Diczfalusy U, Stahle L, Ahlborg G, Wahren J. Cholesterol homeostasis in human brain: turnover of 24-Shydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J Lipid Res 1998; 39: 1594-600.
8. Bogdanovic N, Bretillon L, Lund EG, Diczfalusy U, Lannfelt L, Winblad B, et al. On the turnover of brain cholesterol in patients with Alzheimer's disease. Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells. Neurosci Lett 2001; 314: 45-8.
9. Bondolfi L, Calhoun M, Ermini F, Kuhn HG, Wiederhold KH, Walker L, et al. Amyloid-associated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice. J Neurosci 2002; 22: 515-22.
10. Canevari L, Abramov AY, Duchen MR. Toxicity of amyloid beta peptide: tales of calcium, mitochondria, and oxidative stress. Neurochem Res 2004; 29: 637-50.
11. Casserly I, Topol E. Convergence of atherosclerosis and Alzheimer's disease: inflammation, cholesterol, and misfolded proteins. Lancet 2004; 363: 1139-46.
12. Cataldo AM, Peterhoff CM, Troncoso JC, Gomez-Isla T, Hyman BT, Nixon RA. Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. Am J Pathol 2000; 157: 277-86.
13. Cheruku SR, Xu Z, Dutia R, Lobel P, Storch J. Mechanism of cholesterol transfer from the Niemann-Pick type C2 protein to model membranes supports a role in lysosomal cholesterol transport. J Biol Chem 2006; 281: 31594-604.
14. Cooper NG, McLaughlin BJ. The distribution of filipin-sterol complexes in photoreceptor synaptic membranes. J Comp Neurol 1984; 230: 437-43.
15. Cossec JC, Simon A, Marquer C, Moldrich RX, Leterrier C, Rossier J, et al. Clathrin-dependent APP endocytosis and Abeta secretion are highly sensitive to the level of plasma membrane cholesterol. Biochim Biophys Acta 2010; 1801: 846-52.
16. Cutler RG, Kelly J, Storie K, Pedersen WA, Tammara A, Hatanpaa K, et al. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. Proc Natl Acad Sci USA 2004; 101: 2070-5.
17. Dietschy JM, Turley SD. Cholesterol metabolism in the brain. Curr Opin Lipidol 2001; 12: 105-12.
18. Dietschy JM, Turley SD. Thematic review series: brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal. J Lipid Res 2004; 45: 1375-97.
19. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007; 35: 495-16.
20. Faure A, Verret L, Bozon B, El Tannir El Tayara N, Ly M, et al. Impaired neurogenesis, neuronal loss, and brain functional deficits in the APPxPS1-Ki mouse model of Alzheimer's disease. Neurobiol Aging 2011; 32: 407-18.
21. Feng B, Yao PM, Li Y, Devlin CM, Zhang D, Harding HP, et al The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nat Cell Biol 2003; 5: 781-92.
22. Fox NC, Scahill RI, Crum WR, Rossor MN. Correlation between rates of brain atrophy and cognitive decline in AD. Neurology 1999; 52: 1687-9.
23. Grimm D, Streetz KL, Jopling CL, Storm TA, Pandey K, Davis CR, et al. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 2006; 441: 537-41.
24. Hetz C, Mollereau B. Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases. Nat Rev Neurosci 2014; 15: 233-49.
25. Hoozemans JJ, van Haastert ES, Nijholt DA, Rozemuller AJ, Eikelenboom P, Scheper W. The unfolded protein response is activated in pretangle neurons in Alzheimer's disease hippocampus. Am J Pathol 2009; 174: 1241-51.
26. Hudry E, Van Dam D, Kulik W, De Deyn PP, Stet FS, Ahouansou O, et al. Adeno-associated virus gene therapy with cholesterol 24-hydroxylase reduces the amyloid pathology before or after the onset of amyloid plaques in mouse models of Alzheimer's disease. Mol Ther 2010; 18: 44-53.
27. Infante RE, Wang ML, Radhakrishnan A, Kwon HJ, Brown MS, Goldstein JL. NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes. Proc Natl Acad Sci USA 2008; 105: 15287-92.
28. Ishizuka N, Cowan WM, Amaral DG. A quantitative analysis of the dendritic organization of pyramidal cells in the rat hippocampus. J Comp Neurol 1995; 362: 17-45.
29. Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 2013; 12: 207-16.
30. Lazar AN, Bich C, Panchal M, Desbenoit N, Petit VW, Touboul D, et al. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging reveals cholesterol overload in the cerebral cortex of Alzheimer disease patients. Acta Neuropathol 2013; 125: 133-44.
31. Leal SL, Yassa MA. Perturbations of neural circuitry in aging, mild cognitive impairment, and Alzheimer's disease. Ageing Res Rev 2013; 12: 823-31.
32. Lund EG, Guileyardo JM, Russell DW. cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain. Proc Natl Acad Sci USA 1999; 96: 7238-43.
33. Lund EG, Xie C, Kotti T, Turley SD, Dietschy JM, Russell DW. Knockout of the cholesterol 24-hydroxylase gene in mice reveals a brain-specific mechanism of cholesterol turnover. J Biol Chem 2003; 278: 22980-8.
34. Lutjohann D, Bjorkhem I, Locatelli S, Dame C, Schmolling J, von Bergmann K, et al. Cholesterol dynamics in the foetal and neonatal brain as reflected by circulatory levels of 24S-hydroxycholesterol. Acta Paediatr 2001; 90: 652-7.
35. Lutjohann D, Breuer O, Ahlborg G, Nennesmo I, Siden A, Diczfalusy U, et al. Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation. Proc Natl Acad Sci USA 1996; 93: 9799-804.
36. Marquer C, Devauges V, Cossec JC, Liot G, Lecart S, Saudou F, et al. Local cholesterol increase triggers amyloid precursor protein-Bace1 clustering in lipid rafts and rapid endocytosis. FASEB J 2011; 25: 1295-305.
37. Mattson MP, Partin J, Begley JG. Amyloid beta-peptide induces apoptosis-related events in synapses and dendrites. Brain Res 1998; 807: 167-76.
38. Mondragon-Rodriguez S, Perry G, Zhu X, Moreira PI, Acevedo-Aquino MC, Williams S. Phosphorylation of tau protein as the link between oxidative stress, mitochondrial dysfunction, and connectivity failure: implications for Alzheimer's disease. Oxid Med Cell Longev 2013; 2013: 940603.
39. Mueller SG, Schuff N, Yaffe K, Madison C, Miller B, Weiner MW. Hippocampal atrophy patterns in mild cognitive impairment and Alzheimer's disease. Hum Brain Mapp 2010; 31: 1339-47.
40. Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA, Yuan J. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 2000; 403: 98-103.
41. Oram JF, Lawn RM. ABCA1. The gatekeeper for eliminating excess tissue cholesterol. J Lipid Res 2001; 42: 1173-9.
42. Palmiter RD, Cole TB, Quaife CJ, Findley SD. ZnT-3, a putative transporter of zinc into synaptic vesicles. Proc Natl Acad Sci USA 1996; 93: 14934-9.
43. Pike LJ. Lipid rafts: heterogeneity on the high seas. Biochem J 2004; 378: 281-92.
44. Posse De Chaves EI, Vance DE, Campenot RB, Kiss RS, Vance JE. Uptake of lipoproteins for axonal growth of sympathetic neurons. J Biol Chem 2000; 275: 19883-90.
45. Russell DW, Halford RW, Ramirez DM, Shah R, Kotti T. Cholesterol 24-hydroxylase: an enzyme of cholesterol turnover in the brain. Annu Rev Biochem 2009; 78: 1017-40.
46. Sadleir KR, Bennett DA, Schneider JA, Vassar R. Elevated Abeta42 in aged, non-demented individuals with cerebral atherosclerosis. Curr Alzheimer Res 2013; 10: 785-9.
47. Schroder M, Kaufman RJ. The mammalian unfolded protein response. Annu Rev Biochem 2005; 74: 739-9.
48. Sevin C, Benraiss A, Van Dam D, Bonnin D, Nagels G, Verot L, et al. Intracerebral adeno-associated virus-mediated gene transfer in rapidly progressive forms of metachromatic leukodystrophy. Hum Mol Genet 2006; 15: 53-64.
49. Shafaati M, Olin M, Bavner A, Pettersson H, Rozell B, Meaney S, et al. Enhanced production of 24S-hydroxycholesterol is not sufficient to drive liver X receptor target genes in vivo. J Intern Med 2011; 270: 377-87.
50. Sharpe LJ, Brown AJ. Controlling cholesterol synthesis beyond 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). J Biol Chem 2013; 288: 18707-15.
51. Silvestrini M, Viticchi G, Falsetti L, Balucani C, Vernieri F, Cerqua R, et al. The role of carotid atherosclerosis in Alzheimer's disease progression. J Alzheimers Dis 2011; 25: 719-26.
52. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011; 7: 280-92.
53. Sturchler-Pierrat C, Staufenbiel M. Pathogenic mechanisms of Alzheimer's disease analyzed in the APP23 transgenic mouse model. Ann N Y Acad Sci 2000; 920: 134-9.
54. Tabas I. Consequences of cellular cholesterol accumulation: basic concepts and physiological implications. J Clin Invest 2002; 110:905-11.
55. Thelen KM, Falkai P, Bayer TA, Lutjohann D. Cholesterol synthesis rate in human hippocampus declines with aging. Neurosci Lett 2006; 403: 15-19.
56. Thinakaran G, Koo EH. Amyloid precursor protein trafficking, processing, and function. J Biol Chem 2008; 283: 29615-19.
57. Vance JE. Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases. Dis Model Mech 2012; 5:746-55.
58. Vetrivel KS, Thinakaran G. Amyloidogenic processing of beta-amyloid precursor protein in intracellular compartments. Neurology 2006; 66: S69-73.
59. von Arnim CA, von Einem B, Weber P, Wagner M, Schwanzar D, Spoelgen R, et al. Impact of cholesterol level upon APP and BACE proximity and APP cleavage. Biochem Biophys Res Commun 2008; 370: 207-12.
60. Wendell CR, Waldstein SR, Ferrucci L, O'Brien RJ, Strait JB, Zonderman AB. Carotid atherosclerosis and prospective risk of dementia. Stroke 2012; 43: 3319-24.
61. Xie C, Lund EG, Turley SD, Russell DW, Dietschy JM. Quantitation of two pathways for cholesterol excretion from the brain in normal mice and mice with neurodegeneration. J Lipid Res 2003; 44: 1780-9.