Polymorphism of Alzheimer’s Aβ Amyloid Fibrils and Oligomers

  • Oleg N. AntzutkinEmail author
Reference work entry


An overview of the strategy and experimental solid-state NMR, TEM, STEM, and AFM methods useful for obtaining atomic-level-resolution structural models of Alzheimer’s amyloid-β peptide fibrils and oligomers is presented. Polymorphism of amyloid fibrils and oligomers and the relevance to neurotoxicity is discussed.


Amyloid-beta Alzheimer’s disease Amyloid fibrils and oligomers Supramolecular structure Polymorphism and neurotoxicity Solid-state NMR Atomic force microscopy Electron microscopy Protein engineering Drug design 





Alzheimer’s disease


Atomic force microscopy


Amyloid precursor protein


Nuclear magnetic resonance


Scanning transmission electron microscopy


Transmission electron microscopy



O.N.A. acknowledges financial support from the Foundation in the memory of J.C. and Seth M. Kempe, the Swedish Foundation of International Cooperation in Research and Higher Education (STINT), the Swedish Research Council and the Swedish Alzheimer’s Fund. Collaboration on these projects with R. Tycko, R.D. Leapman, A.A. Sousa, J.J. Balbach, Y. Ishii, A. Petkova, N.W. Rizzo, N.A. Oyler, D.J. Gordon, S.C. Meredith, J. Reed, F. Dyda, F. Delaglio in the U.S.A., with M. Lindberg, N. Almqvist, M. Hellberg, N. Norlin, P. Eriksson, G. Gröbner, A. Filippov, A. Lund, A. Olofsson, T. Härd, C. Lendel, A. Dubnovitsky in Sweden, with M. Bjerring, N.Ch. Nielsen in Denmark, with R. Dupree, S.P. Brown, D. Iuga, R.T. Kelly, J. Becker-Baldus, J.R. Lewandowski, S. Potocki, Ch. Cousins, A. Kukol in the U.K. and with N.V. Shtyrlin and R.S. Pavelyev in Russia are greatly acknowledged.


  1. 1.
    Alzheimer A. On a distinctive disease of the cerebral cortex. Z Psychiatry. 1907;64:146–8.Google Scholar
  2. 2.
  3. 3.
    Selkoe DJ. Amyloid protein and Alzheimer’s disease. Sci Am. 1991;265:68–78.CrossRefGoogle Scholar
  4. 4.
    Glenner GG, Wong CW. Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun. 1984;120:885–9.CrossRefGoogle Scholar
  5. 5.
    Glenner GG, Wong CW. Alzheimer’s disease and Down’s syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun. 1984;122:1131–5.CrossRefGoogle Scholar
  6. 6.
    Masters CL, Multhaup G, Simms G, Pottgiesser J, Martins RN, Beyreuther K. Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer’s disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J. 1985;4:2757–63.CrossRefGoogle Scholar
  7. 7.
    Kang J, Lemaire H-G, Unterbeck A, Salbaum JM, Masters CL, Grzeschik K-H, Multhaup G, Beyreuther K, Müller-Hill B. The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature (London). 1987;325:733–6.CrossRefGoogle Scholar
  8. 8.
    Shivers BD, Hilbich C, Multhaup G, Salbaum M, Beyreuther K, Seeburg PH. Alzheimer’s disease amyloidogenic glycoprotein: expression pattern in rat brain suggests a role in cell contact. EMBO J. 1988;7(5):1365–70.CrossRefGoogle Scholar
  9. 9.
    Marx J. Alzheimer’s debate boils over. Science. 1992;257:1336–8.Google Scholar
  10. 10.
    Dickson DW, Yen SH. Beta-amyloid deposition and paired filament formation: which histopathological feature is more significant in Alzheimer’s disease? Neurobiol Aging. 1989;10:402–4.CrossRefGoogle Scholar
  11. 11.
    Terry RD, Masliah E, Salmon DP, Butters N, de Teresa R, Hill R, Katzman R. Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991;30:572–80.CrossRefGoogle Scholar
  12. 12.
    Selkoe DJ. Deciphering Alzheimer’s disease: molecular genetics and cell biology yield major clues. J NIH Res. 1995;7:57–64.Google Scholar
  13. 13.
    Kayed R, Head E, Thompson JL, McIntire TM, Milton SC, Cotman CW, Glabe CG. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science. 2003;300:486–9.CrossRefGoogle Scholar
  14. 14.
    Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ. Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo. Nature. 2002;416:535–9.CrossRefGoogle Scholar
  15. 15.
    Hendriks L, van Duijn CM, Cras P, Cruts M, Hul WV, van Harskamp F, Warren A, McInnis MG, Antonarakis SE, Martin JJ, Hofman A, Broeckhoven CV. Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the β-amyloid precursor protein gene. Nat Genet. 1992;1:218–21.CrossRefGoogle Scholar
  16. 16.
    Levy E, Carman MD, Fernandez-Madrid IJ, Power MD, Lieberburg I, van Duinen SG, Bots GAM, Luyendijk W, Frangione B. Mutation of the Alzheimer’s disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science. 1990;248:1124–6.CrossRefGoogle Scholar
  17. 17.
    Tagliavini F, Rossi G, Padovani A, Magoni M, Andora G, Sgarzi M, Bizzi A, Savoiardo M, Carella F, Morbin M, Giaccone G, Bugiani O. A new APP mutation related to hereditary cerebral haemorrhage. Alz Report. 1999;2:S28.Google Scholar
  18. 18.
    Nilsberth C, Westlind-Danielsson A, Eckman CB, Condron MM, Axelman K, Forsell C, Stenh C, Luthman J, Teplow DB, Yonkin SG, Näslund J, Lannfelt L. The “Arctic” APP mutation (E693G) causes Alzheimer’s disease by enhanced Aβ protofibril formation. Nat Neurosci. 2001;4(9):887–93.CrossRefGoogle Scholar
  19. 19.
    Grabowski TJ, Cho HS, Vonsattel JPG, Rebeck GW, Greenberg SM. Novel amyloid precursor protein mutation in an Iowa family with dementia and severe cerebral amyloid angiopathy. Ann Neurol. 2001;49:697–705.CrossRefGoogle Scholar
  20. 20.
    Takuma H, Teraoka R, Mori H, Tomiyama T. Amyloid-β E22Δ variant induces synaptic alteration in mouse hippocampal slices. Neuroreport. 2008;19:615–9.CrossRefGoogle Scholar
  21. 21.
    Kirkitadze MD, Condron MM, Teplow DB. Identification and characterization of key kinetic intermediates in amyloid β- protein fibrillogenesis. J Mol Biol. 2001;312:1103–19.CrossRefGoogle Scholar
  22. 22.
    Antzutkin ON. Amyloidosis of Alzheimer’s Aβ-peptides: solid-state nuclear magnetic resonance, electron paramagnetic resonance, transmission electron microscopy, scanning transmission electron microscopy and atomic force microscopy studies. Magn Reson Chem. 2004;42:231–46.CrossRefGoogle Scholar
  23. 23.
    Hellberg M, Norlin N, Antzutkin ON, Almqvist N. Morphology and growth kinetics of Alzheimer’s amyloid β-peptides, Aβ(1–40) and the “Arctic” mutation Aβ(1–40)(E22G): in-situ atomic force microscopy study. In: Grateau G, Kyle RA, Skinner M, editors. Amyloid and amyloidosis. Boca Raton: CRC Press; 2005. p. 408–10.CrossRefGoogle Scholar
  24. 24.
    Norlin N, Hellberg M, Filippov A, Sousa AA, Grobner G, Leapman RD, Almqvist N, Antzutkin ON. Aggregation and fibril morphology of the “Arctic” mutation of Alzheimer’s Aβ peptide by CD, TEM, STEM and in situ AFM. J Struct Biol. 2012;180:174–89.CrossRefGoogle Scholar
  25. 25.
    Sisodia SS, Koo EH, Beyreuther K, Unterbeck A, Price DL. Evidence that β-amyloid protein in Alzheimer’s disease is not derived by normal processing. Science. 1990;248:492–5.CrossRefGoogle Scholar
  26. 26.
    Buxbaum JD, Gandy SE, Ciccetti P, Ehrlich ME, Czernik AJ, Fracasso RP, Ramabhadran TV, Unterbeck AJ, Greengard P. Processing of Alzheimer β/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation. Proc Natl Acad Sci U S A. 1990;87:6003–6.CrossRefGoogle Scholar
  27. 27.
    Pike CJ, Burdick D, Walencewicz AJ, Glabe GC, Cotman CW. Neurodegeneration induced by β-amyloid peptides in vitro: the role of peptide assembly state. J Neurosci. 1993;13(4):1676–87.CrossRefGoogle Scholar
  28. 28.
    Lorenzo A, Yankner B. β-amyloid neurotoxicity requires fibril formation and is inhibited by Congo red. Proc Natl Acad Sci U S A. 1994;91:12243–7.CrossRefGoogle Scholar
  29. 29.
    Howlett DR, Jennings KH, Lee DC, Clark MS, Brown F, Wetzel R, Wood SJ, Camilleri P, Roberts GW. Aggregation state and neurotoxic properties of Alzheimer beta-amyloid peptide. Neurodegeneration. 1995;4:23–32.CrossRefGoogle Scholar
  30. 30.
    Petkova AT, Leapman RD, Guo Z, Yau W-M, Mattson MP, Tycko R. Self-propagating, molecular-level polymorphism in Alzheimer’s β-amyloid fibrils. Science. 2005;307:262–5.CrossRefGoogle Scholar
  31. 31.
    Seilheimer B, Bohrmann B, Bondolfi L, Müller F, Stüber D, Döbeli H. The toxicity of the Alzheimer’s β-amyloid peptide correlates with a distinct fiber morphology. J Struct Biol. 1997;119:59–71.CrossRefGoogle Scholar
  32. 32.
    Sandberg A, Luheshi LM, Söllvander S, de Barros TP, Macao B, Knowles TP, Biverstål H, Lendel C, Ekholm-Petterson F, Dubnovitsky A, Lannfelt L, Dobson CM, Härd T. Stabilization of neurotoxic Alzheimer amyloid-β oligomers by protein engineering. Proc Natl Acad Sci U S A. 2010;107:15595–600.CrossRefGoogle Scholar
  33. 33.
    Castaño EM, Ghiso J, Prelli F, Gorevic PD, Migheli A, Frangione B. In vitro formation of amyloid fibrils from two synthetic peptides of different lengths homologous to Alzheimer’s disease β-protein. Biochem Biophys Res Commun. 1986;141:782–9.CrossRefGoogle Scholar
  34. 34.
    Gorevic PC, Castaño EM, Sarma R, Frangione B. Ten to fourteen residue peptides of Alzheimer’s disease protein are sufficient for amyloid fibril formation and its characteristic X-ray diffraction pattern. Biochem Biophys Res Commun. 1987;147:854–62.CrossRefGoogle Scholar
  35. 35.
    Kirschner DA, Inouye H, Duffy LK, Sinclair A, Lind M, Selkoe DJ. Synthetic peptide homologous to β-protein from Alzheimer disease forms amyloid-like fibers in vitro. Proc Natl Acad Sci U S A. 1987;84:6953–7.CrossRefGoogle Scholar
  36. 36.
    Halverson K, Fraser P, Kirschner DA, Lansbury Jr PT. Molecular determinants of amyloid deposition in Alzheimer’s disease: conformational studies of synthetic β-protein fragments. Biochemistry. 1990;29:2639–44.CrossRefGoogle Scholar
  37. 37.
    Fraser PE, Duffy LK, O’Malley MB, Nguyen JT, Inouye H, Kirschner DA. Morphology and antibody recognition of synthetic beta-amyloid peptides. J Neurosci Res. 1991;28:474–85.CrossRefGoogle Scholar
  38. 38.
    Fraser PE, Nguyen JT, Surewicz WK, Kirschner DA. pH-dependent structural transitions of Alzheimer amyloid β/A4 peptides. Biophys J. 1991;60:1190–201.CrossRefGoogle Scholar
  39. 39.
    Fraser PE, McLachlan DR, Surewicz WK, Mizzen CA, Snow AD, Nguyen JT, Kirschner DA. Conformation and fibrillogenesis of Alzheimer Aβ peptides with selected substitution of charged residues. J Mol Biol. 1994;244:64–73.CrossRefGoogle Scholar
  40. 40.
    Hilbich C, Kisters-Woike B, Reed J, Masters CL, Beyreuthers K. Aggregation and secondary structure of synthetic amyloid βA4 peptides of Alzheimer’s disease. J Mol Biol. 1991;218:149–63.CrossRefGoogle Scholar
  41. 41.
    Hilbich C, Kisters-Woike B, Reed J, Masters CL, Beyreuthers K. Human and rodent sequence analogs of Alzheimer’s amyloid βA4 share similar properties and can be solubilized in buffers of pH 7.4. Eur J Biochem. 1991;201:61–9.CrossRefGoogle Scholar
  42. 42.
    Hilbich C, Kisters-Woike B, Reed J, Masters CL, Beyreuthers K. Substitutions of hydrophobic amino acids reduce the amyloidogenicity of Alzheimer’s disease βA4 peptides. J Mol Biol. 1992;228:460–73.CrossRefGoogle Scholar
  43. 43.
    Barrow CJ, Zagorski MG. Solution structures of β peptide and its constituent fragments: relation to amyloid deposition. Science. 1991;253:179–82.CrossRefGoogle Scholar
  44. 44.
    Barrow CJ, Yasuda A, Kenny PTM, Zagorski MG. Solution conformations and aggregational properties of synthetic amyloid β-peptides of Alzheimer’s disease. Analysis of circular dichroism spectra. J Mol Biol. 1992;225:1075–93.CrossRefGoogle Scholar
  45. 45.
    Burdick D, Soreghan B, Kwon M, Kosmoski J, Knauer M, Henschen A, Yates J, Cotman C, Glabe C. Assembly and aggregation properties of synthetic Alzheimer’s A4/β amyloid peptide analogs. J Biol Chem. 1992;267:546–54.Google Scholar
  46. 46.
    Malinchik SB, Inouye H, Szumowski KE, Kirschner DA. Structural analysis of Alzheimer’s β(1-40) amyloid: protofilament assembly of tubular fibrils. Biophys J. 1998;74:537–45.CrossRefGoogle Scholar
  47. 47.
    Serpell LC, Blake CCF, Fraser PE. Molecular structure of a fibrillar Alzheimer’s Aβ fragment. Biochemistry. 2000;39:13269–75.CrossRefGoogle Scholar
  48. 48.
    Serpell LC, Smith JM. Direct visualization of the β-sheet structure of synthetic Alzheimer’s amyloid. J Mol Biol. 2000;299:225–31.CrossRefGoogle Scholar
  49. 49.
    Lansbury PT, Costa PR, Griffiths JM, Simon EJ, Auger M, Halverson KJ, Kocisko DA, Hendsch ZS, Ashburn TT, Spencer RGS, Tidor B, Griffin RG. Structural model for the β-amyloid fibril based on interstrand alignment of an antiparallel β-sheet comprising a C-terminal peptide. Nat Struct Biol. 1995;2:990–8.CrossRefGoogle Scholar
  50. 50.
    Kirschner DA, Abraham CR, Selkoe DJ. X-ray diffraction from intraneuronal paired helical filaments and extraneuronal amyloid fibers in Alzheimer disease indicated cross-β conformation. Proc Natl Acad Sci U S A. 1987;83:503–7.CrossRefGoogle Scholar
  51. 51.
    Roher AE, Lowenson JD, Clarke S, Woods AS, Cotter RJ, Gowing E, Ball MJ. β-amyloid-(1–42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease. Proc Natl Acad Sci U S A. 1993;90:10836–40.CrossRefGoogle Scholar
  52. 52.
    Paravastu AK, Qahwash I, Leapman RD, Meredith SC, Tycko R. Seeded growth of β-amyloid fibrils from Alzheimer’s brain-derived fibrils produces a distinct structure. Proc Natl Acad Sci U S A. 2009;106:7443–8.CrossRefGoogle Scholar
  53. 53.
    Lu J-X, Qiang W, Yau W-M, Schwieters CD, Meredith SC, Tycko R. Molecular structure of β-amyloid fibrils in Alzheimer’s disease brain tissue. Cell. 2013;154:1257–68.CrossRefGoogle Scholar
  54. 54.
    Antzutkin ON, Leapman RD, Rizzo NW, Balbach JJ, Tycko R. Supramolecular structural constraints on Alzheimers β-amyloid fibrils from electron microscopy and solid-state nuclear magnetic resonance. Biochemistry. 2002;41:15436–50.CrossRefGoogle Scholar
  55. 55.
    Goldsbury CS, Wirtz S, Müller SA, Sunderji S, Wicki P, Aebi U, Frey P. Studies on the in vitro assembly of Aβ(1–40): implications for the search for Aβ fibril formation inhibitors. J Struct Biol. 2000;130:217–31.CrossRefGoogle Scholar
  56. 56.
    Engel A, Baumeister W, Saxton WO. Mass mapping of a protein complex with the scanning transmission electron microscope. Proc Natl Acad Sci U S A. 1982;79:4050–4.CrossRefGoogle Scholar
  57. 57.
    Wall JS, Hainfeld JF. Mass mapping with the scanning transmission electron microscope. Annu Rev Biophys Biophys Chem. 1986;15:355–76.CrossRefGoogle Scholar
  58. 58.
    Müller SA, Goldie KN, Burki R, Haring R, Engel A. Factors influencing the precision of quantitative scanning transmission electron microscopy. Ultramicroscopy. 1992;46:317–334.59.CrossRefGoogle Scholar
  59. 59.
    Thomas D, Schultz P, Steven AC, Wall JS. Mass analysis of biological macromolecular complexes by STEM. Biol Cell. 1994;80:181–92.CrossRefGoogle Scholar
  60. 60.
    Chen B, Thurber KR, Shewmaker F, Wickner RB, Tycko R. Measurement of amyloid fibril mass-per-length by tilted-beam transmission electron microscopy. Proc Natl Acad Sci U S A. 2009;106:14339–44.CrossRefGoogle Scholar
  61. 61.
    Benzinger TLS, Gregory DM, Burkoth TS, Miller-Auer H, Lynn DG, Botto RE, Meredith SC. Propagating structure of Alzheimer’s β-amyloid(10−35) is parallel β-sheet with residues in exact register. Proc Natl Acad Sci U S A. 1998;95:13407–12.CrossRefGoogle Scholar
  62. 62.
    Gregory DM, Benzinger TLS, Burkoth TS, Miller-Auer H, Lynn DG, Meredith SC, Botto RE. Dipolar recoupling NMR of biomolecular self-assemblies: determining inter- and intrastrand distances in fibrilized Alzheimer’s β-amyloid peptide. Solid State Nucl Magn Reson. 1998;13:149–66.CrossRefGoogle Scholar
  63. 63.
    Burkoth TS, Benzinger TLS, Urban V, Morgan DM, Gregory DM, Thiyagarajan P, Botto RE, Meredith SC, Lynn DG. Structure of the β-amyloid(10–35) fibril. J Am Chem Soc. 2000;122:7883–9.CrossRefGoogle Scholar
  64. 64.
    Benzinger TLS, Gregory DM, Burkoth TS, Miller-Auer H, Lynn DG, Botto RE, Meredith SC. Two-dimensional structure of β-amyloid(10–35) fibrils. Biochemistry. 2000;39:3491–9.CrossRefGoogle Scholar
  65. 65.
    Antzutkin ON. Molecular structure determination: applications in biology. In: Duer MJ, editor. Solid-state nuclear magnetic resonance spectroscopy, principles and application. Oxford: Blackwell Science; 2002. p. 280–390.Google Scholar
  66. 66.
    Tycko R. Insight into amyloid folding problem from solid-state NMR. Biochemistry. 2003;42(11):3151–9.CrossRefGoogle Scholar
  67. 67.
    Tycko R. Application of solid-state NMR to the structural characterization of amyloid fibrils: methods and results. Prog Nucl Magn Reson Spectrosc. 2003;42:53–68.CrossRefGoogle Scholar
  68. 68.
    Petkova AT, Ishii Y, Balbach JJ, Antzutkin ON, Leapman RD, Delaglio F, Tycko R. A structural model for Alzheimer’s β-amyloid fibrils based on experimental constraints from solid state NMR. Proc Natl Acad Sci U S A. 2002;99(2):16742–7.CrossRefGoogle Scholar
  69. 69.
    Bertini I, Gonnelli L, Luchinat C, Mao J, Nesi A. A new structural model of Aβ40 fibrils. J Am Chem Soc. 2011;133:16013–22.CrossRefGoogle Scholar
  70. 70.
    Antzutkin ON, Tycko R. High-order multiple quantum excitation in 13C nuclear magnetic resonance spectroscopy of organic solids. J Chem Phys. 1999;110(6):2749–52.CrossRefGoogle Scholar
  71. 71.
    Antzutkin ON, Balbach JJ, Leapman RD, Rizzo NW, Reed J, Tycko R. Multiple quantum solid state NMR indicates a parallel, not antiparallel, organization of β-sheets in Alzheimer’s β-amyloid fibrils. Proc Natl Acad Sci U S A. 2000;97(24):13045–50.CrossRefGoogle Scholar
  72. 72.
    Ishii Y, Balbach JJ, Tycko R. Measurement of dipole-coupled lineshapes in a many-spin system by constant-time two-dimensional solid state NMR with high-speed magic-angle-spinning. Chem Phys. 2001;266:231–6.CrossRefGoogle Scholar
  73. 73.
    Balbach JJ, Petkova AT, Oyler NA, Antzutkin ON, Gordon DJ, Meredith SC, Tycko R. Supramolecular structure in full-length of Alzheimer’s β-amyloid fibrils: evidence for a parallel β-sheet organization from solid state nuclear magnetic resonance. Biophys J. 2002;83(2):1205–16.CrossRefGoogle Scholar
  74. 74.
    Weliky DP, Tycko R. Determination of peptide conformations by two-dimensional magic angle spinning NMR exchange spectroscopy with rotor synchronization. J Am Chem Soc. 1996;118:8487–8.CrossRefGoogle Scholar
  75. 75.
    Balbach JJ, Ishii Y, Antzutkin ON, Leapman RD, Rizzo NW, Dyda F, Reed J, Tycko R. Amyloid fibril formation by Aβ(16–22), a seven-residue fragment of the Alzheimer’s β-amyloid peptide, and structural characterization by solid state NMR. Biochemistry. 2000;39(45):13748–59.CrossRefGoogle Scholar
  76. 76.
    Antzutkin ON, Balbach JJ, Tycko R. Site-specific identification of non-β-strand conformations in Alzheimer’s β-amyloid fibrils by solid state NMR. Biophys J. 2003;84(5):3326–35.CrossRefGoogle Scholar
  77. 77.
    Blanco FJ, Tycko R. Determination of peptide backbone dihedral angles in solid-state NMR by double quantum 13C chemical shift anisotropy measurements. J Magn Reson. 2001;149:131–8.CrossRefGoogle Scholar
  78. 78.
    Tycko R. Selection rules for multiple quantum NMR excitation in solids: derivation from time-reversal symmetry and comparisons with simulations and 13C NMR experiments. J Magn Reson. 1999;139:302–7.CrossRefGoogle Scholar
  79. 79.
    Oyler NA, Tycko R. Multiple quantum 13C NMR spectroscopy in solids under high-speed magic-angle-spinning. J Phys Chem B. 2002;106:8382–9.CrossRefGoogle Scholar
  80. 80.
    Antzutkin ON, Iuga D, Filippov AV, Kelly RT, Becker-Baldus J, Brown SP, Dupree R. Hydrogen bonding in Alzheimer’s amyloid-β fibrils probed by 15N{17O}REAPDOR solid state NMR. Angew Chem Int Ed. 2012;51(41):10289–92.CrossRefGoogle Scholar
  81. 81.
    Wei J, Antzutkin ON, Filippov AV, Iuga D, Lam PY, Barrow MP, Dupree R, Brown SP, O’Connor PB. Amyloid hydrogen bonding polymorphism evaluated by 15N{17O}REAPDOR solid-state NMR and ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry. Biochemistry. 2016;55:2065–8.CrossRefGoogle Scholar
  82. 82.
    Petkova AT, Yau WM, Tycko R. Experimental constraints on quaternary structure in Alzheimer’s β-amyloid fibrils. Biochemistry. 2006;45(2):498–512.CrossRefGoogle Scholar
  83. 83.
    Xiao Y, Ma B, McElheny D, Parthasarathy S, Long F, Hoshi M, Nussinov R, Ishii Y. Aβ(1–42) fibril structure illuminates self-recognition and replication of amyloid in Alzheimer’s disease. Nat Struct Mol Biol. 2015;22(6):499–505.CrossRefGoogle Scholar
  84. 84.
    Colvin MT, Silvers R, Frohm B, Su Y, Linse S, Griffin RG. High resolution structural characterization of Aβ42 amyloid fibrils by magic angle spinning NMR. J Am Chem Soc. 2015;137(23):7509–18.CrossRefGoogle Scholar
  85. 85.
    Aulikki-Walti M, Ravotti F, Arai H, Glabe CG, Wall JS, Böckmann A, Güntert P, Meier BH, Riek R. Atomic-resolution structure of a disease-relevant Aβ(1–42) amyloid fibril. Proc Natl Acad Sci U S A. 2016;113(34):E4976–84.CrossRefGoogle Scholar
  86. 86.
    Elkins MR, Wang T, Nick M, Jo H, Lemmin T, Prusiner SB, DeGrado WF, Stöhr J, Hong M. Structural polymorphism of Alzheimer’s β-amyloid fibrils as controlled by an E22 switch: a solid-state NMR study. J Am Chem Soc. 2016;138(31):9840–52.CrossRefGoogle Scholar
  87. 87.
    Tjernberg LO, Näslund J, Lindqvist F, Johansson J, Karlström AR, Thyberg J, Terenius L, Nordstedt C. Arrest of β-amyloid fibril formation by a pentapeptide ligand. J Biol Chem. 1996;271(15):8545–8.CrossRefGoogle Scholar
  88. 88.
    Selkoe DJ. Cell biology of protein misfolding: the examples of Alzheimer’s and Parkinson’s diseases. Nat Cell Biol. 2004;6(11):1054–61.CrossRefGoogle Scholar
  89. 89.
    Lendel C, Bjerring M, Dubnovitsky A, Kelly RT, Filippov A, Antzutkin ON, Nielsen NCh, Härd T. A hexameric peptide barrel as building block of amyloid-β protofibrils. Angew Chem Int Ed. 2014;53:12756–60.CrossRefGoogle Scholar
  90. 90.
    Wang T, Jo H, DeGrado WF, Hong M. Water distribution, dynamics, and interactions with Alzheimer’s β-amyloid fibrils investigated by solid-state NMR. J Am Chem Soc. 2017.
  91. 91.
    Potocki S, Cousins Ch, Filippov AV, Shtyrlin NV, Pavelyev RS, Antzutkin ON, Lewandowski JR. Insights into specific interaction of Alzheimer’s β-amyloid toxic oligomers with 13C carbonyl labelled curcumin. In: 58th experimental nuclear magnetic resonance conference, Asilomar, Pacific Grove, 26–31 Mar 2017.Google Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Chemistry of InterfacesLuleå University of TechnologyLuleåSweden

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