Amyloid-β(1-2) Protofibrils Formed in Modified Artificial Cerebrospinal Fluid Bind and Activate Microglia

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• 作者：Geeta S. Paranjape (1)
  Shana E. Terrill (1)
  Lisa K. Gouwens (1)
  Benjamin M. Ruck (1)
  Michael R. Nichols (1) (2)
  
• 关键词：Amyloid ; beta protein ; Aggregation ; Protofibrils ; Microglia ; Inflammation
• 刊名：Journal of Neuroimmune Pharmacology
• 出版年：2013
• 出版时间：March 2013
• 年：2013
• 卷：8
• 期：1
• 页码：312-322
• 全文大小：507KB
• 参考文献：1. Bamberger ME, Harris ME, McDonald DR, Husemann J, Landreth GE (2003) A cell surface receptor complex for fibrillar β-amyloid mediates microglial activation. J Neurosci 23:2665-674
  2. Bitan G, Kirkitadze MD, Lomakin A, Vollers SS, Benedek GB, Teplow DB (2003) Amyloid β-protein (Aβ) assembly: Aβ40 and Aβ42 oligomerize through distinct pathways. Proc Natl Acad Sci USA 100:330-35 CrossRef
  3. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248-54 CrossRef
  4. Cleary JP, Walsh DM, Hofmeister JJ, Shankar GM, Kuskowski MA, Selkoe DJ, Ashe KH (2005) Natural oligomers of the amyloid-β protein specifically disrupt cognitive function. Nat Neurosci 8:79-4 CrossRef
  5. Combs CK, Karlo JC, Kao SC, Landreth GE (2001) β-amyloid stimulation of microglia and monocytes results in TNFα-dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J Neurosci 21:1179-188
  6. Dahlgren KN, Manelli AM, Stine WB Jr, Baker LK, Krafft GA, LaDu MJ (2002) Oligomeric and fibrillar species of amyloid-β peptides differentially affect neuronal viability. J Biol Chem 277:32046-2053 CrossRef
  7. Dickson DW (2004) Apoptotic mechanisms in Alzheimer neurofibrillary degeneration: cause or effect? J Clin Invest 114:23-7
  8. Dickson DW, Lee SC, Mattiace LA, Yen SHC, Brosnan C (1993) Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer disease. Glia 7:75-3 CrossRef
  9. Fassbender K, Walter S, Kuhl S, Landmann R, Ishii K, Bertsch T, Stalder AK, Muehlhauser F, Liu Y, Ulmer AJ, Rivest S, Lentschat A, Gulbins E, Jucker M, Staufenbiel M, Brechtel K, Walter J, Multhaup G, Penke B, Adachi Y, Hartmann T, Beyreuther K (2004) The LPS receptor (CD14) links innate immunity with Alzheimer’s disease. FASEB J 18:203-05
  10. Georganopoulou DG, Chang L, Nam JM, Thaxton CS, Mufson EJ, Klein WL, Mirkin CA (2005) Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer’s disease. Proc Natl Acad Sci USA 102:2273-276 CrossRef
  11. Gravina SA, Ho L, Eckman CB, Long KE, Otvos L Jr, Younkin LH, Suzuki N, Younkin SG (1995) Amyloid β protein (Aβ) in Alzheimer’s disease brain. Biochemical and immunocytochemical analysis with antibodies specific for forms ending at Aβ40 or Aβ42(43). J Biol Chem 270:7013-016 CrossRef
  12. Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid β-peptide. Nat Rev Mol Cell Biol 8:101-12 CrossRef
  13. Harper JD, Wong SS, Lieber CM, Lansbury PT Jr (1997) Observation of metastable Aβ amyloid protofibrils by atomic force microscopy. Chem Biol 4:119-25 CrossRef
  14. Harper JD, Wong SS, Lieber CM, Lansbury PT Jr (1999) Assembly of Aβ amyloid peptides: an in vitro model for a possible early event in Alzheimer’s disease. Biochemistry 38:8972-980 CrossRef
  15. Hartley DM, Walsh DM, Ye CP, Diehl T, Vasquez S, Vassilev PM, Teplow DB, Selkoe DJ (1999) Protofibrillar intermediates of amyloid β-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons. J Neurosci 19:8876-884
  16. Jan A, Hartley DM, Lashuel HA (2010) Preparation and characterization of toxic Aβ aggregates for structural and functional studies in Alzheimer’s disease research. Nat Protoc 5:1186-209 CrossRef
  17. Jarrett JT, Berger EP, Lansbury PT Jr (1993) The carboxy terminus of the β amyloid protein is critical for the seeding of amyloid formation: Implications for the pathogenesis of Alzheimer’s disease. Biochemistry 32:4693-697 CrossRef
  18. Jin M, Shepardson N, Yang T, Chen G, Walsh D, Selkoe DJ (2011) Soluble amyloid β-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration. Proc Natl Acad Sci USA 108:5819-824 CrossRef
  19. Kayed R, Head E, Thompson JL, McIntire TM, Milton SC, Cotman CW, Glabe CG (2003) Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300:486-89 CrossRef
  20. Kheterpal I, Lashuel HA, Hartley DM, Walz T, Lansbury PT Jr, Wetzel R (2003) Aβ protofibrils possess a stable core structure resistant to hydrogen exchange. Biochemistry 42:14092-4098 CrossRef
  21. Lee EB, Leng LZ, Zhang B, Kwong L, Trojanowski JQ, Abel T, Lee VM (2006) Targeting amyloid-β peptide (Aβ) oligomers by passive immunization with a conformation-selective monoclonal antibody improves learning and memory in Aβ precursor protein (APP) transgenic mice. J Biol Chem 281:4292-299 CrossRef
  22. Liu S, Liu Y, Hao W, Wolf L, Kiliaan AJ, Penke B, Rube CE, Walter J, Heneka MT, Hartmann T, Menger MD, Fassbender K (2012) TLR2 Is a primary receptor for Alzheimer’s amyloid β peptide to trigger neuroinflammatory activation. J Immunol 188:1098-107 CrossRef
  23. McGeer EG, McGeer PL (1998) The importance of inflammatory mechanisms in Alzheimer disease. Exp Gerontol 33:371-78 CrossRef
  24. McGeer PL, Itagaki S, Tago H, McGeer EG (1987) Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR. Neurosci Lett 79:195-00 CrossRef
  25. McNay EC, Gold PE (1999) Extracellular glucose concentrations in the rat hippocampus measured by zero-net-flux: effects of microdialysis flow rate, strain, and age. J Neurochem 72:785-90 CrossRef
  26. Meda L, Cassatella MA, Szendrei GI, Otvos L Jr, Baron P, Villalba M, Ferrari D, Rossi F (1995) Activation of microglial cells by β-amyloid protein and interferon-γ. Nature 374:647-50 CrossRef
  27. Nichols MR, Moss MA, Reed DK, Lin WL, Mukhopadhyay R, Hoh JH, Rosenberry TL (2002) Growth of β-amyloid(1-0) protofibrils by monomer elongation and lateral association. Characterization of distinct products by light scattering and atomic force microscopy. Biochemistry 41:6115-127 CrossRef
  28. O’Nuallain B, Freir DB, Nicoll AJ, Risse E, Ferguson N, Herron CE, Collinge J, Walsh DM (2010) Amyloid β-protein dimers rapidly form stable synaptotoxic protofibrils. J Neurosci 30:14411-4419 CrossRef
  29. Paranjape GS, Gouwens LK, Osborn DC, Nichols MR (2012) Isolated amyloid-β(1-2) protofibrils, but not isolated fibrils, are robust stimulators of microglia. ACS Chem Neurosci 3:302-11 CrossRef
  30. Reed-Geaghan EG, Savage JC, Hise AG, Landreth GE (2009) CD14 and Toll-like receptors 2 and 4 are required for fibrillar Aβ-stimulated microglial activation. J Neurosci 29:11982-1992 CrossRef
  31. Selkoe DJ (2004) Cell biology of protein misfolding: The examples of Alzheimer’s and Parkinson’s diseases. Nat Cell Biol 6:1054-061 CrossRef
  32. Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J, Halle A, Rayner KJ, Boyer L, Zhong R, Frazier WA, Lacy-Hulbert A, Khoury JE, Golenbock DT, Moore KJ (2010) CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol 11:155-61 CrossRef
  33. Tzounopoulos T, Kim Y, Oertel D, Trussell LO (2004) Cell-specific, spike timing-dependent plasticities in the dorsal cochlear nucleus. Nat Neurosci 7:719-25 CrossRef
  34. Udan ML, Ajit D, Crouse NR, Nichols MR (2008) Toll-like receptors 2 and 4 mediate Aβ(1-2) activation of the innate immune response in a human monocytic cell line. J Neurochem 104:524-33
  35. Walsh DM, Selkoe DJ (2007) Aβ oligomers - a decade of discovery. J Neurochem 101:1172-184 CrossRef
  36. Walsh DM, Lomakin A, Benedek GB, Condron MM, Teplow DB (1997) Amyloid β-protein fibrillogenesis: detection of a protofibrillar intermediate. J Biol Chem 272:22364-2372 CrossRef
  37. Walsh DM, Hartley DM, Kusumoto Y, Fezoui Y, Condron MM, Lomakin A, Benedek GB, Selkoe DJ, Teplow DB (1999) Amyloid β-protein fibrillogenesis: structure and biological activity of protofibrillar intermediates. J Biol Chem 274:25945-5952 CrossRef
  38. Ye CP, Selkoe DJ, Hartley DM (2003) Protofibrils of amyloid β-protein inhibit specific K⁺ currents in neocortical cultures. Neurobiol Dis 13:177-90 CrossRef
  
• 作者单位：Geeta S. Paranjape (1)
  Shana E. Terrill (1)
  Lisa K. Gouwens (1)
  Benjamin M. Ruck (1)
  Michael R. Nichols (1) (2)
  
  1. Department of Chemistry and Biochemistry and Center for Nanoscience, University of Missouri-St. Louis, St. Louis, MO, USA
  2. Department of Chemistry and Biochemistry, University of Missouri-St. Louis, One University Boulevard, St. Louis, MO, 63121, USA
  
• ISSN：1557-1904

文摘

Soluble aggregated forms of amyloid-β protein (Aβ) have garnered significant attention recently for their role in Alzheimer’s disease (AD). Protofibrils are a subset of these soluble species and are considered intermediates in the aggregation pathway to mature Aβ fibrils. Biological studies have demonstrated that protofibrils exhibit both toxic and inflammatory activities. It is important in these in vitro studies to prepare protofibrils using solution conditions that are appropriate for cellular studies as well as conducive to biophysical characterization of protofibrils. Here we describe the preparation and characterization of Aβ(1-2) protofibrils in modified artificial cerebrospinal fluid (aCSF) and demonstrate their prominent binding and activation of microglial cells. A simple phosphate/bicarbonate buffer system was prepared that maintained the ionic strength and cell compatibility of F-12 medium but did not contain numerous supplements that interfere with spectroscopic analyses of Aβ protofibrils. Reconstitution of Aβ(1-2) in aCSF and isolation with size exclusion chromatography (SEC) revealed curvilinear β-sheet protofibrils <100?nm in length and hydrodynamic radii of 21?nm. Protofibril concentration determination by BCA assay, which was not possible in F-12 medium, was more accurately measured in aCSF. Protofibrils formed and isolated in aCSF, but not monomers, markedly stimulated TNFα production in BV-2 and primary microglia and bound in significant amounts to microglial membranes. This report demonstrates the suitability of a modified aCSF system for preparing SEC-isolated Aβ(1-2) protofibrils and underscores the unique ability of protofibrils to functionally interact with microglia.