Processing of endogenous AβPP in blood-brain barrier endothelial cells is modulated by liver-x receptor agonists and altered cellular cholesterol homeostasis

Journal of Alzheimer's Disease

Volumn 27, Issue 2, 2011, Pages 341-360

  Schweinzer, Cornelia ^a   Kober, Alexandra ^a   Lang, Ingrid ^a   Etschmaier, Karoline ^a   Scholler, Monika ^a   Kresse, Adelheid ^a   Sattler, Wolfgang ^a   Panzenboeck, Ute ^a  

^a MEDICAL UNIVERSITY OF GRAZ   (Austria)

Author keywords

Alzheimer's disease; amyloid ; blood brain barrier; cholesterol; endothelial cells; liver X receptors; oxysterols; statins

Indexed keywords

24 HYDROXYCHOLESTEROL; ABC TRANSPORTER A1; AMYLOID PRECURSOR PROTEIN; CHOLESTEROL; CHOLESTEROL ACYLTRANSFERASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; LIVER X RECEPTOR; LIVER X RECEPTOR AGONIST; MEVALONIC ACID; N (2,2,2 TRIFLUOROETHYL) N [4 (2,2,2 TRIFLUORO 1 HYDROXY 1 TRIFLUOROMETHYLETHYL)PHENYL]BENZENESULFONAMIDE; OXYSTEROL; SIMVASTATIN; STEROL REGULATORY ELEMENT BINDING PROTEIN 2; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BASOLATERAL MEMBRANE; BLOOD BRAIN BARRIER; BRAIN CAPILLARY; CHOLESTEROL ESTERIFICATION; CHOLESTEROL METABOLISM; CHOLESTEROL SYNTHESIS; DOWN REGULATION; ENDOTHELIUM CELL; GENE EXPRESSION; HOMEOSTASIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROCESSING; PROTEIN SECRETION; PROTEIN SYNTHESIS;

EID: 81855168382     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-2011-110854     Document Type: Article

References (73)

1. Burns A, Byrne EJ, Maurer K (2002) Alzheimer's disease. Lancet 360, 163-165. (Pubitemid 34786210)
2. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science 297, 353-356. (Pubitemid 34790756)
3. Morris JC (1997) Clinical assessment of Alzheimer's disease. Neurology 49, S7-S10. (Pubitemid 27391791)
4. Repetto E, Russo C, Venezia V, Nizzari M, Nitsch RM, Schettini G (2004) BACE1 overexpression regulates amyloid precursor protein cleavage and interaction with the ShcA adapter. Ann N Y Acad Sci 1030, 330-338. (Pubitemid 40378930)
5. De Strooper B (2003) Aph-1, Pen-2, and Nicastrin with Pre-senilin generate an active gamma-Secretase complex. Neuron 38, 9-12.
6. Haass C, Selkoe DJ (1993) Cellular processing of beta-amyloid precursor protein and the genesis of amyloid beta-peptide. Cell 75, 1039-1042.
7. Selkoe DJ (1996) Amyloid beta-protein and the genetics of Alzheimer's disease. J Biol Chem 271, 18295-18298. (Pubitemid 26322675)
8. Corrigan F, Pham CL, Vink R, Blumbergs PC, Masters CL, van den Heuvel C, Cappai R (2011) The neuroprotective domains of the amyloid precursor protein, in traumatic brain injury, are located in the two growth factor domains. Brain Res 1378, 137-143.
9. Vincent B (2004) ADAM proteases: Protective role in Alzheimer's and prion diseases? Curr Alzheimer Res 1, 165-174.
10. Anstey KJ, Lipnicki DM, Low LF (2008) Cholesterol as a risk factor for dementia and cognitive decline: A systematic review of prospective studies with meta-analysis. Am J Geriatr Psychiatry 16, 343-354.
11. Pfrieger FW (2003) Cholesterol homeostasis and function in neurons of the central nervous system. Cell Mol Life Sci 60, 1158-1171. (Pubitemid 36791918)
12. DeKosky ST (2005) Statin therapy in the treatment of Alzheimer disease: What is the rationale? Am J Med 118 Suppl 12A, 48-53.
13. Buxbaum JD, Cullen EI, Friedhoff LT (2002) Pharmacological concentrations of the HMG-CoA reductase inhibitor lovastatin decrease the formation of the Alzheimer beta-amyloid peptide in vitro and in patients. Front Biosci 7, a50-a59.
14. Wolozin B (2004) Cholesterol and the biology of Alzheimer's disease. Neuron 41, 7-10. (Pubitemid 38068431)
15. Refolo LM, Malester B, LaFrancois J, Bryant-Thomas T, Wang R, Tint GS, Sambamurti K, Duff K, Pappolla MA (2000) Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiol Dis 7, 321-331.
16. Bodovitz S, Klein WL (1996) Cholesterol modulates alpha-secretase cleavage of amyloid precursor protein. J Biol Chem 271, 4436-4440.
17. Ehehalt R, Keller P, Haass C, Thiele C, Simons K (2003) Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts. J Cell Biol 160, 113-123. (Pubitemid 36091721)
18. Hartmann T, Bieger SC, Bruhl B, Tienari PJ, Ida N, All-sop D, Roberts GW, Masters CL, Dotti CG, Unsicker K, Beyreuther K (1997) Distinct sites of intracellular production for Alzheimer's disease Abeta40/42 amyloid peptides. Nat Med 3, 1016-1020. (Pubitemid 27391957)
19. Vetrivel KS, Cheng H, Lin W, Sakurai T, Li T, Nukina N, Wong PC, Xu H, Thinakaran G (2004) Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranes. J Biol Chem 279, 44945-44954. (Pubitemid 39430908)
20. Hutter-Paier B, Huttunen HJ, Puglielli L, Eckman CB, Kim DY, Hofmeister A, Moir RD, Domnitz SB, Frosch MP, Windisch M, Kovacs DM (2004) The ACAT inhibitor CP-113, 818 markedly reduces amyloid pathology in a mouse model of Alzheimer's disease. Neuron 44, 227-238. (Pubitemid 39346248)
21. Huttunen HJ, Greco C, Kovacs DM (2007) Knockdown of ACAT-1 reduces amyloidogenic processing of APP. FEBS Lett 581, 1688-1692. (Pubitemid 46546584)
22. Puglielli L, Ellis BC, Ingano LA, Kovacs DM (2004) Role of acyl-coenzyme A: cholesterol acyltransferase activity in the processing of the amyloid precursor protein. J Mol Neurosci 24, 93-96. (Pubitemid 41359173)
23. Sun Y, Yao J, Kim TW, Tall AR (2003) Expression of liver X receptor target genes decreases cellular amyloid beta peptide secretion. J Biol Chem 278, 27688-27694. (Pubitemid 36899957)
24. Hirsch-Reinshagen V, Maia LF, Burgess BL, Blain JF, Naus KE, McIsaac SA, Parkinson PF, Chan JY, Tansley GH, Hay-den MR, Poirier J, Van Nostrand W, Wellington CL (2005) The absence of ABCA1 decreases soluble ApoE levels but does not diminish amyloid deposition in two murine models of Alzheimer disease. J Biol Chem 280, 43243-43256. (Pubitemid 43049291)
25. Koldamova RP, Lefterov IM, Staufenbiel M, Wolfe D, Huang S, Glorioso JC, Walter M, Roth MG, Lazo JS (2005) The liver X receptor ligand T0901317 decreases amyloid beta production in vitro and in a mouse model of Alzheimer's disease. J Biol Chem 280, 4079-4088. (Pubitemid 40288571)
26. Wahrle SE, Jiang H, Parsadanian M, Hartman RE, Bales KR, Paul SM, Holtzman DM (2005) Deletion of Abca1 increases Abeta deposition in the PDAPP transgenic mouse model of Alzheimer disease. J Biol Chem 280, 43236-43242. (Pubitemid 43049290)
27. Dietschy JM, Turley SD (2001) Cholesterol metabolism in the brain. Curr Opin Lipidol 12, 105-112. (Pubitemid 32242918)
28. Bjorkhem I, Lutjohann D, Breuer O, Sakinis A, Wennmalm A (1997) Importance of a novel oxidative mechanism for elimination of brain cholesterol. Turnover of cholesterol and 24 (S)-hydroxycholesterol in rat brain as measured with 18O2 techniques in vivo and in vitro. J Biol Chem 272, 30178-30184. (Pubitemid 27512218)
29. Heverin M, Bogdanovic N, Lutjohann D, Bayer T, Pikuleva I, Bretillon L, Diczfalusy U, Winblad B, Bjorkhem I (2004) Changes in the levels of cerebral and extracerebral sterols in the brain of patients with Alzheimer's disease. J Lipid Res 45, 186-193. (Pubitemid 38180529)
30. Edmond J (2001) Essential polyunsaturated fatty acids and the barrier to the brain: The components of a model for transport. J Mol Neurosci 16, 181-193; discussion 215-121. (Pubitemid 32664778)
31. Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ (1996) An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 383, 728-731. (Pubitemid 26360651)
32. Brown MS, Goldstein JL (1997) The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 89, 331-340. (Pubitemid 27220877)
33. Martins IJ, Berger T, Sharman MJ, Verdile G, Fuller SJ, Martins RN (2009) Cholesterol metabolism and transport in the pathogenesis ofAlzheimer's disease. J Neurochem111, 1275-1308.
34. Kim WS, Chan SL, Hill AF, Guillemin GJ, Garner B (2009) Impact of 27-hydroxycholesterol on amyloid-beta peptide production and ATP-binding cassette transporter expression in primary human neurons. J Alzheimers Dis 16, 121-131.
35. Burns MP, Vardanian L, Pajoohesh-Ganji A, Wang L, Cooper M, Harris DC, Duff K, Rebeck GW (2006) The effects of ABCA1 on cholesterol efflux and Abeta levels in vitro and in vivo. J Neurochem 98, 792-800. (Pubitemid 44051280)
36. Riddell DR, Zhou H, Comery TA, Kouranova E, Lo CF, Warwick HK, Ring RH, Kirksey Y, Aschmies S, Xu J, Kubek K, Hirst WD, Gonzales C, Chen Y, Murphy E, Leonard S, Vasy-lyev D, Oganesian A, Martone RL, Pangalos MN, Reinhart PH, Jacobsen JS (2007) The LXR agonist TO901317 selectively lowers hippocampal Abeta42 and improves memory in the Tg2576 mouse model of Alzheimer's disease. Mol Cell Neurosci 34, 621-628. (Pubitemid 46483091)
37. Hirsch-Reinshagen V, Burgess BL, Wellington CL (2009) Why lipids are important for Alzheimer disease? Mol Cell Biochem 326, 121-129.
38. Begley DJ, Brightman MW (2003) Structural and functional aspects of the blood-brain barrier. Prog Drug Res 61, 39-78. (Pubitemid 37187402)
39. Deane R, Du Yan S, Submamaryan RK, LaRue B, Jovanovic S, Hogg E, Welch D, Manness L, Lin C, Yu J, Zhu H, Ghiso J, Frangione B, Stern A, Schmidt AM, Armstrong DL, Arnold B, Liliensiek B, Nawroth P, Hofman F, Kindy M, Stern D, Zlokovic B (2003) RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med 9, 907-913. (Pubitemid 36889934)
40. Shibata M, Yamada S, Kumar SR, Calero M, Bading J, Fran-gione B, Holtzman DM, Miller CA, Strickland DK, Ghiso J, Zlokovic BV (2000) Clearance of Alzheimer's amyloid-ss (1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Invest 106, 1489-1499. (Pubitemid 32038587)
41. Panzenboeck U, Balazs Z, Sovic A, Hrzenjak A, Levak-Frank S, Wintersperger A, Malle E, Sattler W (2002) ABCA1 and scavenger receptor class B, type I, are modulators of reverse sterol transport at an in vitro blood-brain barrier constituted of porcine brain capillary endothelial cells. J Biol Chem 277, 42781-42789. (Pubitemid 35285652)
42. Panzenboeck U, Kratzer I, Sovic A, Wintersperger A, Bern-hart E, Hammer A, Malle E, Sattler W (2006) Regulatory effects of synthetic liver X receptor-and peroxisome-proliferator activated receptor agonists on sterol transport pathways in polarized cerebrovascular endothelial cells. Int J Biochem Cell Biol 38, 1314-1329.
43. Tewes B. FH, Hellwig S, Hoheisel D, Decker S, Griesche G, Tilling T, Wegener J, Galla HJ (1997) Preparation of endothe-lial cells in primary cultures obtained from brains of 6-month old pigs. In Drug Transport Across the Blood-Brain Barrier (BBB): in Vivo and in Vitro Techniques W. dBAGaS, ed. Harwood Academic, Amsterdam pp. 91-97.
44. Larionov A, Krause A, Miller W (2005) A standard curve based method for relative real time PCR data processing. BMC Bioinformatic 6, 62.
45. Pussinen PJ, Karten B, Wintersperger A, Reicher H, McLean M, Malle E, Sattler W (2000) The human breast carcinoma cell line HBL-100 acquires exogenous cholesterol from high-density lipoprotein via CLA-1 (CD-36 and LIMPII analogous 1)-mediated selective cholesteryl ester uptake. Biochem J349, 559-566. (Pubitemid 30465791)
46. Candela P, Gosselet F, Saint-Pol J, Sevin E, Boucau MC, Boulanger E, Cecchelli R, Fenart L (2010) Apical-to-basolateral transport of amyloid-fj peptides through blood-brain barrier cells is mediated by the receptor for advanced glycation end-products and is restricted by P-glycoprotein. J Alzheimers Dis 22, 849-859.
47. Horton JD, Shimomura I, Brown MS, Hammer RE, Goldstein JL, Shimano H (1998) Activation of cholesterol synthesis in preference to fatty acid synthesis in liver and adipose tissue of transgenic mice overproducing sterol regulatory element-binding protein-2. J Clin Invest 101, 2331-2339. (Pubitemid 28270427)
48. Wong J, Quinn CM, Brown AJ (2006) SREBP-2 positively regulates transcription of the cholesterol efflux gene, ABCA1, by generating oxysterol ligands forLXR. Biochem J 400, 485-491. (Pubitemid 44974460)
49. Zeng L, Liao H, Liu Y, Lee TS, Zhu M, Wang X, Ste-merman MB, Zhu Y, Shyy JY (2004) Sterol-responsive element-binding protein (SREBP) 2 down-regulates ATP-binding cassette transporter A1 in vascular endothelial cells: A novel role of SREBP in regulating cholesterol metabolism. J Biol Chem 279, 48801-48807. (Pubitemid 39625759)
50. Mason JC (2003) Statins and their role in vascular protection. Clin Sci (Lond) 105, 251-266. (Pubitemid 37088562)
51. Werner N, Nickenig G, Laufs U (2002) Pleiotropic effects of HMG-CoA reductase inhibitors. Basic Res Cardiol 97, 105-116. (Pubitemid 34223500)
52. Cole SL, Grudzien A, Manhart IO, Kelly BL, Oakley H, Vassar R (2005) Statins cause intracellular accumulation of amyloid precursor protein, beta-secretase-cleaved fragments, and amyloid beta-peptide via an isoprenoid-dependent mechanism. J Biol Chem 280, 18755-18770. (Pubitemid 41379577)
53. Zelcer N, Khanlou N, Clare R, Jiang Q, Reed-Geaghan EG, Landreth GE, Vinters HV, Tontonoz P (2007) Attenuation of neuroinflammation and Alzheimer's disease pathology by liver x receptors. Proc Natl Acad Sci USA 104, 10601-10606. (Pubitemid 47185711)
54. Zlokovic BV (2010) Neurodegeneration and the neurovascular unit. Nat Med 16, 1370-1371.
55. Crossgrove JS, Smith EL, Zheng W (2007) Macromolecules involved in production and metabolism of beta-amyloid at the brain barriers. Brain Res 1138, 187-195. (Pubitemid 46281881)
56. Forloni G, Demicheli F, Giorgi S, Bendotti C, Angeretti N (1992) Expression of amyloid precursor protein mRNAs in endothelial, neuronal and glial cells: modulation by interleukin-1. Brain Res Mol Brain Res 16, 128-134.
57. Simons ER, Marshall DC, Long HJ, Otto K, Billingslea A, Tibbles H, Wells J, Eisenhauer P, Fine RE, Cribbs DH, Davies TA, Abraham CR (1998) Blood brain barrier endothelial cells express candidate amyloid precursor protein-cleaving secre-tases. Amyloid 5, 153-162. (Pubitemid 128699443)
58. LaFerla FM, Green KN, Oddo S (2007) Intracellular amyloid-beta in Alzheimer's disease. Nat Rev Neurosci 8, 499-509.
59. Abildayeva K, Jansen PJ, Hirsch-Reinshagen V, Bloks VW, Bakker AH, Ramaekers FC, de Vente J, Groen AK, Wellington CL, Kuipers F, Mulder M (2006) 24 (S)-hydroxycholesterol participates in a liver X receptor-controlled pathway in astrocytes that regulates apolipoprotein E-mediated cholesterol efflux. J Biol Chem 281, 12799-12808. (Pubitemid 43855372)
60. Cartagena CM, Burns MP, Rebeck GW (2010) 24S-hydroxycholesterol effects on lipid metabolism genes are modeled in traumatic brain injury. Brain Res 1319, 1-12.
61. Chawla A, Repa JJ, Evans RM, Mangelsdorf DJ (2001) Nuclear receptors and lipid physiology: Opening the X-files. Science 294, 1866-1870. (Pubitemid 33101573)
62. Wang Y, Muneton S, Sjovall J, Jovanovic JN, Griffiths WJ (2008) The effect of 24S-hydroxycholesterol on cholesterol homeostasis in neurons: Quantitative changes to the cortical neuron proteome. J Proteome Res 7, 1606-1614.
63. Wang Y, Rogers PM, Su C, Varga G, Stayrook KR, Burris TP (2008) Regulation of cholesterologenesis by the oxysterol receptor, LXRalpha. J Biol Chem 283, 26332-26339.
64. Kojro E, Fuger P, Prinzen C, Kanarek AM, Rat D, Endres K, Fahrenholz F, Postina R (2010) Statins and the squalene synthase inhibitor zaragozic acid stimulate the non-amyloidogenic pathway of amyloid-beta protein precursor processing by suppression of cholesterol synthesis. J Alzheimers Dis 20, 1215-1231.
65. Nelson TJ, Alkon DL (2005) Insulin and cholesterol pathways in neuronal function, memory and neurodegeneration. Biochem Soc Trans 33, 1033-1036. (Pubitemid 41659107)
66. Prasanthi JR, Huls A, Thomasson S, Thompson A, Schommer E, Ghribi O (2009) Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on beta-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells. Mol Neurodegene 4, 1.
67. Kojro E, Gimpl G, Lammich S, Marz W, Fahrenholz F (2001) Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the alpha-secretase ADAM 10. Proc Natl Acad Sci USA 98, 5815-5820. (Pubitemid 32435725)
68. Ostrowski SM, Wilkinson BL, Golde TE, Landreth G (2007) Statins reduce amyloid-beta production through inhibition of protein isoprenylation. J Biol Chem 282, 26832-26844. (Pubitemid 47501902)
69. Famer D, Meaney S, Mousavi M, Nordberg A, Bjorkhem I, Crisby M (2007) Regulation of alpha-and beta-secretase activity by oxysterols: Cerebrosterol stimulates processing of APP via the alpha-secretase pathway. Biochem Biophys Res Commun 359, 46-50. (Pubitemid 46844819)
70. Puglielli L, Konopka G, Pack-Chung E, Ingano LA, Bere-zovska O, Hyman BT, Chang TY, Tanzi RE, Kovacs DM (2001) Acyl-coenzyme A: Cholesterol acyltransferase modulates the generation of the amyloid beta-peptide. Nat Cell Biol 3, 905-912. (Pubitemid 32952255)
71. Huttunen HJ, Havas D, Peach C, Barren C, Duller S, Xia W, Frosch MP, Hutter-Paier B, Windisch M, Kovacs DM (2010) The acyl-coenzyme A: Cholesterol acyltransferase inhibitor CI-1011 reverses diffuse brain amyloid pathology in aged amyloidprecursor protein transgenic mice. J Neuropathol Exp Neurol 69, 777-788.
72. Koldamova R, Fitz NF, Lefterov I (2010) The role of ATP-binding cassette transporter A1 in Alzheimer's disease and neurodegeneration. Biochim Biophys Acta 1801, 824-830.
73. Koldamova R, Staufenbiel M, Lefterov I (2005) Lack of ABCA1 considerably decreases brain ApoE level and increases amyloid deposition in APP23 mice. J Biol Chem 280, 43224-43235. (Pubitemid 43049289)