Advertisement

The Protein Journal

, Volume 38, Issue 4, pp 425–434 | Cite as

Structure and Function of Alzheimer’s Amyloid βeta Proteins from Monomer to Fibrils: A Mini Review

  • Nikhil AgrawalEmail author
  • Adam A. SkeltonEmail author
Article

Abstract

Alzheimer’s disease is the most common form of dementia, that affects millions of people worldwide. According to the widely accepted amyloid cascade hypothesis, misfolding and aggregation of Aβ peptides is the principal cause of Alzheimer’s disease. In the present mini-review, we have discussed the different structures of Aβ protein from monomer to fibrils and their arrangement in different symmetries. We have highlighted the critical amino acid residue that plays a crucial role in the early stage misfolding of Aβ monomers, Aβ fibrils arrangement in different symmetries, the elongation process and Aβ protein interaction with the membrane. We have further discussed the antibodies that are currently in clinical trial phase III for Alzheimer’s disease.

Keywords

Alzheimer’s disease Amyloid βeta peptide Solanezumab Bapineuzumab Tramiprosate 

Notes

Acknowledgements

N.A. would like to thank College of Health Sciences, UKZN, South Africa for providing Honorary Research Fellow position, and We would like to thank Centre of High performance (CHPC), Cape Town, South Africa for computational resources. We want to thank Prof. Thirumala Govender for proofreading support and Charlotte Ramadhin for proofreading the manuscript.

References

  1. 1.
    Uflacker A, Doraiswamy PM (2017) Alzheimer’s disease: an overview of recent developments and a look to the future. Focus 15(1):13–17CrossRefGoogle Scholar
  2. 2.
    Alzheimer’s Association (2016) 2016 Alzheimer’s disease facts and figures. Alzheimer’s Dement 12(4):459–509CrossRefGoogle Scholar
  3. 3.
    Wimo A, Guerchet M, Ali G-C, Wu Y-T, Prina AM, Winblad B, Jönsson L, Liu Z, Prince M (2017) The worldwide costs of dementia 2015 and comparisons with 2010. Alzheimer’s Dement 13(1):1–7CrossRefGoogle Scholar
  4. 4.
    Patterson C (2018) World Alzheimer Report 2018 The state of the art of dementia research: new frontiersGoogle Scholar
  5. 5.
    Tarawneh R, Holtzman DM (2012) The clinical problem of symptomatic Alzheimer disease and mild cognitive impairment. Cold Spring Harb Perspect Med 2(5):a006148PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Herrup K (2015) The case for rejecting the amyloid cascade hypothesis. Nat Neurosci 18(6):794PubMedCrossRefGoogle Scholar
  7. 7.
    Bali J, Halima SB, Felmy B, Goodger Z, Zurbriggen S, Rajendran L (2010) Cellular basis of Alzheimer’s disease. Ann Indian Acad Neurol 13(Suppl2):S89PubMedPubMedCentralGoogle Scholar
  8. 8.
    Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297(5580):353–356PubMedCrossRefGoogle Scholar
  9. 9.
    Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science 256(5054):184CrossRefPubMedGoogle Scholar
  10. 10.
    Karran E, Mercken M, De Strooper B (2011) The amyloid cascade hypothesis for Alzheimer’s disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov 10(9):698PubMedCrossRefGoogle Scholar
  11. 11.
    Reitz C (2012) Alzheimer’s disease and the amyloid cascade hypothesis: a critical review. Int J Alzheimer’s Dis 2012:11Google Scholar
  12. 12.
    Armstrong RA (2014) A critical analysis of the ‘amyloid cascade hypothesis’. Folia Neuropathol 52(3):211–225PubMedCrossRefGoogle Scholar
  13. 13.
    Sipe JD, Cohen AS (2000) History of the amyloid fibril. J Struct Biol 130(2–3):88–98PubMedCrossRefGoogle Scholar
  14. 14.
    O’Brien RJ, Wong PC (2011) Amyloid precursor protein processing and Alzheimer’s disease. Annu Rev Neurosci 34:185–204PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Del Prete D, Checler F, Chami M (2014) Ryanodine receptors: physiological function and deregulation in Alzheimer disease. Mol Neurodegen 9(1):21CrossRefGoogle Scholar
  16. 16.
    Spies PE, Verbeek MM, van Groen T, Claassen J (2012) Reviewing reasons for the decreased CSF Abeta42 concentration in Alzheimer disease. Front Biosci 17:2024–2034CrossRefGoogle Scholar
  17. 17.
    Bergström P, Agholme L, Nazir FH, Satir TM, Toombs J, Wellington H, Strandberg J, Bontell TO, Kvartsberg H, Holmström M (2016) Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation. Sci Rep 6:29200PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Glenner GG, Wong CW (1984) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120(3):885–890PubMedCrossRefGoogle Scholar
  19. 19.
    Yoshiike Y, Chui D-H, Akagi T, Tanaka N, Takashima A (2003) Specific compositions of amyloid-β peptides as the determinant of toxic β-aggregation. J Biol Chem 278(26):23648–23655PubMedCrossRefGoogle Scholar
  20. 20.
    Uversky VN (2009) Intrinsic disorder in proteins associated with neurodegenerative diseases. Protein folding and misfolding: neurodegenerative diseases. Springer, Dordrecht, pp 21–75CrossRefGoogle Scholar
  21. 21.
    Ball KA, Phillips AH, Nerenberg PS, Fawzi NL, Wemmer DE, Head-Gordon T (2011) Homogeneous and heterogeneous tertiary structure ensembles of amyloid-β peptides. Biochemistry 50(35):7612–7628PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Coles M, Bicknell W, Watson AA, Fairlie DP, Craik DJ (1998) Solution structure of amyloid β-peptide (1–40) in a water–micelle environment. Is the membrane-spanning domain where we think it is? Biochemistry 37(31):11064–11077PubMedCrossRefGoogle Scholar
  23. 23.
    Crescenzi O, Tomaselli S, Guerrini R, Salvadori S, D’Ursi AM, Temussi PA, Picone D (2002) Solution structure of the Alzheimer amyloid β-peptide (1–42) in an apolar microenvironment: similarity with a virus fusion domain. Eur J Biochem 269(22):5642–5648PubMedCrossRefGoogle Scholar
  24. 24.
    Janek K, Rothemund S, Gast K, Beyermann M, Zipper J, Fabian H, Bienert M, Krause E (2001) Study of the conformational transition of Aβ (1–42) using d-amino acid replacement analogues. Biochemistry 40(18):5457–5463PubMedCrossRefGoogle Scholar
  25. 25.
    Vivekanandan S, Brender JR, Lee SY, Ramamoorthy A (2011) A partially folded structure of amyloid-beta (1–40) in an aqueous environment. Biochem Biophys Res Commun 411(2):312–316PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Tomaselli S, Esposito V, Vangone P, van Nuland NA, Bonvin AM, Guerrini R, Tancredi T, Temussi PA, Picone D (2006) The α-to-β conformational transition of Alzheimer’s Aβ-(1–42) peptide in aqueous media is reversible: a step by step conformational analysis suggests the location of β conformation seeding. ChemBioChem 7(2):257–267PubMedCrossRefGoogle Scholar
  27. 27.
    Luttmann E, Fels G (2006) All-atom molecular dynamics studies of the full-length β-amyloid peptides. Chem Phys 323(1):138–147CrossRefGoogle Scholar
  28. 28.
    Agrawal N, Skelton AA (2017) Binding of 12-crown-4 with Alzheimer’s Aβ40 and Aβ42 monomers and its effect on their conformation: insight from molecular dynamics simulations. Mol Pharm 15(1):289–299PubMedCrossRefGoogle Scholar
  29. 29.
    Valerio M, Colosimo A, Conti F, Giuliani A, Grottesi A, Manetti C, Zbilut JP (2005) Early events in protein aggregation: molecular flexibility and hydrophobicity/charge interaction in amyloid peptides as studied by molecular dynamics simulations. Proteins: Struct Funct Bioinform 58(1):110–118CrossRefGoogle Scholar
  30. 30.
    Miyashita N, Straub JE, Thirumalai D (2009) Structures of β-amyloid peptide 1–40, 1–42, and 1–55—the 672–726 fragment of APP—in a membrane environment with implications for interactions with γ-secretase. J Am Chem Soc 131(49):17843–17852PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Fändrich M (2012) Oligomeric intermediates in amyloid formation: structure determination and mechanisms of toxicity. J Mol Biol 421(4–5):427–440PubMedCrossRefGoogle Scholar
  32. 32.
    Kayed R, Lasagna-Reeves CA (2013) Molecular mechanisms of amyloid oligomers toxicity. J Alzheimer’s Dis 33(s1):S67–S78CrossRefGoogle Scholar
  33. 33.
    Baglioni S, Casamenti F, Bucciantini M, Luheshi LM, Taddei N, Chiti F, Dobson CM, Stefani M (2006) Prefibrillar amyloid aggregates could be generic toxins in higher organisms. J Neurosci 26(31):8160–8167PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Narayan P, Meehan S, Carver JA, Wilson MR, Dobson CM, Klenerman D (2012) Amyloid-β oligomers are sequestered by both intracellular and extracellular chaperones. Biochemistry 51(46):9270–9276PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    He Y, Zheng M-M, Ma Y, Han X-J, Ma X-Q, Qu C-Q, Du Y-F (2012) Soluble oligomers and fibrillar species of amyloid β-peptide differentially affect cognitive functions and hippocampal inflammatory response. Biochem Biophys Res Commun 429(3–4):125–130PubMedCrossRefGoogle Scholar
  36. 36.
    Nimmrich V, Grimm C, Draguhn A, Barghorn S, Lehmann A, Schoemaker H, Hillen H, Gross G, Ebert U, Bruehl C (2008) Amyloid β oligomers (Aβ1–42 globulomer) suppress spontaneous synaptic activity by inhibition of P/Q-type calcium currents. J Neurosci 28(4):788–797PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Yu L, Edalji R, Harlan JE, Holzman TF, Lopez AP, Labkovsky B, Hillen H, Barghorn S, Ebert U, Richardson PL (2009) Structural characterization of a soluble amyloid β-peptide oligomer. Biochemistry 48(9):1870–1877PubMedCrossRefGoogle Scholar
  38. 38.
    Pham JD, Chim N, Goulding CW, Nowick JS (2013) Structures of oligomers of a peptide from β-amyloid. J Am Chem Soc 135(33):12460–12467PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Spencer RK, Li H, Nowick JS (2014) X-ray crystallographic structures of trimers and higher-order oligomeric assemblies of a peptide derived from Aβ17–36. J Am Chem Soc 136(15):5595–5598PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Benilova I, Karran E, De Strooper B (2012) The toxic Aβ oligomer and Alzheimer’s disease: an emperor in need of clothes. Nat Neurosci 15(3):349PubMedCrossRefGoogle Scholar
  41. 41.
    Roychaudhuri R, Yang M, Hoshi MM, Teplow DB (2009) Amyloid β-protein assembly and Alzheimer disease. J Biol Chem 284(8):4749–4753PubMedCrossRefGoogle Scholar
  42. 42.
    Morris KL, Serpell LC (2012) X-ray fibre diffraction studies of amyloid fibrils. Springer, In Amyloid proteins, pp 121–135Google Scholar
  43. 43.
    Scheidt HA, Morgado I, Rothemund S, Huster D (2012) Dynamics of amyloid β fibrils revealed by solid-state NMR. J Biol Chem 287(3):2017–2021PubMedCrossRefGoogle Scholar
  44. 44.
    Anderson VL, Webb WW (2011) Transmission electron microscopy characterization of fluorescently labelled amyloid β 1-40 and α-synuclein aggregates. BMC Biotechnol 11(1):125PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Schmidt M, Rohou A, Lasker K, Yadav JK, Schiene-Fischer C, Fändrich M, Grigorieff N (2015) Peptide dimer structure in an Aβ (1–42) fibril visualized with cryo-EM. Proc Natl Acad Sci 112(38):11858–11863PubMedCrossRefGoogle Scholar
  46. 46.
    Parbhu A, Lin H, Thimm J, Lal R (2002) Imaging real-time aggregation of amyloid beta protein (1–42) by atomic force microscopy. Peptides 23(7):1265–1270PubMedCrossRefGoogle Scholar
  47. 47.
    Buchete N-V, Hummer G (2007) Structure and dynamics of parallel β-sheets, hydrophobic core, and loops in Alzheimer’s Aβ fibrils. Biophys J 92(9):3032–3039PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Inouye H, Fraser PE, Kirschner DA (1993) Structure of beta-crystallite assemblies formed by Alzheimer beta-amyloid protein analogues: analysis by x-ray diffraction. Biophys J 64(2):502–519PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Sunde M, Serpell LC, Bartlam M, Fraser PE, Pepys MB, Blake CC (1997) Common core structure of amyloid fibrils by synchrotron X-ray diffraction1. J Mol Biol 273(3):729–739PubMedCrossRefGoogle Scholar
  50. 50.
    Kirschner DA, Abraham C, Selkoe DJ (1986) X-ray diffraction from intraneuronal paired helical filaments and extraneuronal amyloid fibers in Alzheimer disease indicates cross-beta conformation. Proc Natl Acad Sci 83(2):503–507PubMedCrossRefGoogle Scholar
  51. 51.
    Nilsson MR (2004) Techniques to study amyloid fibril formation in vitro. Methods 34(1):151–160PubMedCrossRefGoogle Scholar
  52. 52.
    Nasica-Labouze J, Nguyen PH, Sterpone F, Berthoumieu O, Buchete N-V, Coté SB, De Simone A, Doig AJ, Faller P, Garcia A (2015) Amyloid β protein and Alzheimer’s disease: when computer simulations complement experimental studies. Chem Rev 115(9):3518–3563PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Paravastu AK, Leapman RD, Yau W-M, Tycko R (2008) Molecular structural basis for polymorphism in Alzheimer’s β-amyloid fibrils. Proc Natl Acad Sci 105(47):18349–18354PubMedCrossRefGoogle Scholar
  54. 54.
    Petkova AT, Ishii Y, Balbach JJ, Antzutkin ON, Leapman RD, Delaglio F, Tycko R (2002) A structural model for Alzheimer’s β-amyloid fibrils based on experimental constraints from solid state NMR. Proc Natl Acad Sci 99(26):16742–16747PubMedCrossRefGoogle Scholar
  55. 55.
    Riek R, Eisenberg DS (2016) The activities of amyloids from a structural perspective. Nature 539(7628):227PubMedCrossRefGoogle Scholar
  56. 56.
    Agrawal N, Skelton AA (2016) 12-crown-4 ether disrupts the patient brain-derived amyloid-β-fibril trimer: insight from all-atom molecular dynamics simulations. ACS Chem Neurosci 7(10):1433–1441PubMedCrossRefGoogle Scholar
  57. 57.
    Xiao Y, Ma B, McElheny D, Parthasarathy S, Long F, Hoshi M, Nussinov R, Ishii Y (2015) Aβ (1–42) fibril structure illuminates self-recognition and replication of amyloid in Alzheimer’s disease. Nat Struct Mol Biol 22(6):499PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Colvin MT, Silvers R, Ni QZ, Can TV, Sergeyev I, Rosay M, Donovan KJ, Michael B, Wall J, Linse S (2016) Atomic resolution structure of monomorphic Aβ42 amyloid fibrils. J Am Chem Soc 138(30):9663–9674PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Wälti MA, Ravotti F, Arai H, Glabe CG, Wall JS, Böckmann A, Güntert P, Meier BH, Riek R (2016) Atomic-resolution structure of a disease-relevant Aβ (1–42) amyloid fibril. Proc Natl Acad Sci 113(34):E4976–E4984PubMedCrossRefGoogle Scholar
  60. 60.
    Gremer L, Schölzel D, Schenk C, Reinartz E, Labahn J, Ravelli RB, Tusche M, Lopez-Iglesias C, Hoyer W, Heise H (2017) Fibril structure of amyloid-β (1–42) by cryo–electron microscopy. Science 358(6359):116–119PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Watanabe-Nakayama T, Ono K, Itami M, Takahashi R, Teplow DB, Yamada M (2016) High-speed atomic force microscopy reveals structural dynamics of amyloid β1–42 aggregates. Proc Natl Acad Sci 113:5835–5840PubMedCrossRefGoogle Scholar
  62. 62.
    Derreumaux P (2013) Alzheimer’s Disease: insights into low molecular weight and cytotoxic aggregates from in vitro and computer experiments: molecular basis of amyloid-beta protein aggregation and fibril formation. World Sci 7:464Google Scholar
  63. 63.
    Masman MF, Eisel UL, Csizmadia IG, Penke B, Enriz RD, Marrink SJ, Luiten PG (2009) In silico study of full-length amyloid β 1–42 tri-and penta-oligomers in solution. J Phys Chem B 113(34):11710–11719PubMedCrossRefGoogle Scholar
  64. 64.
    Lemkul JA, Bevan DR (2010) Assessing the stability of Alzheimer’s amyloid protofibrils using molecular dynamics. J Phys Chem B 114(4):1652–1660PubMedCrossRefGoogle Scholar
  65. 65.
    Lührs T, Ritter C, Adrian M, Riek-Loher D, Bohrmann B, Döbeli H, Schubert D, Riek R (2005) 3D structure of Alzheimer’s amyloid-β (1–42) fibrils. Proc Natl Acad Sci 102(48):17342–17347PubMedCrossRefGoogle Scholar
  66. 66.
    Xu Z, Paparcone R, Buehler MJ (2010) Alzheimer’s Aβ (1-40) amyloid fibrils feature size-dependent mechanical properties. Biophys J 98(10):2053–2062PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Wu C, Bowers MT, Shea J-E (2010) Molecular structures of quiescently grown and brain-derived polymorphic fibrils of the Alzheimer amyloid Aβ9-40 peptide: a comparison to agitated fibrils. PLoS Comput Biol 6(3):e1000693PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Xi W, Wang W, Abbott G, Hansmann UH (2016) Stability of a recently found triple-β-stranded Aβ1–42 fibril motif. J Phys Chem B 120(20):4548–4557PubMedCrossRefGoogle Scholar
  69. 69.
    Miller Y, Ma B, Nussinov R (2011) The unique Alzheimer’s β-amyloid triangular fibril has a cavity along the fibril axis under physiological conditions. J Am Chem Soc 133(8):2742–2748PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Dong M, Zhao W, Hu D, Ai H, Kang B (2017) N-terminus binding preference for either tanshinone or analogue in both inhibition of amyloid aggregation and disaggregation of preformed amyloid fibrils—toward introducing a kind of novel anti-alzheimer compounds. ACS Chem Neurosci 8(7):1577–1588PubMedCrossRefGoogle Scholar
  71. 71.
    Lu J-X, Qiang W, Yau W-M, Schwieters CD, Meredith SC, Tycko R (2013) Molecular structure of β-amyloid fibrils in Alzheimer’s disease brain tissue. Cell 154(6):1257–1268PubMedCrossRefGoogle Scholar
  72. 72.
    Tycko R (2014) Physical and structural basis for polymorphism in amyloid fibrils. Protein Sci 23(11):1528–1539PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Elkins MR, Wang T, Nick M, Jo H, Lemmin T, Prusiner SB, DeGrado WF, Stöhr J, Hong M (2016) Structural polymorphism of Alzheimer’s β-amyloid fibrils as controlled by an E22 switch: a solid-state NMR study. J Am Chem Soc 138(31):9840–9852PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Colletier J-P, Laganowsky A, Landau M, Zhao M, Soriaga AB, Goldschmidt L, Flot D, Cascio D, Sawaya MR, Eisenberg D (2011) Molecular basis for amyloid-β polymorphism. Proc Natl Acad Sci 108(41):16938–16943PubMedCrossRefGoogle Scholar
  75. 75.
    Tycko R (2015) Amyloid polymorphism: structural basis and neurobiological relevance. Neuron 86(3):632–645PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Hubin E, Van Nuland N, Broersen K, Pauwels K (2014) Transient dynamics of Aβ contribute to toxicity in Alzheimer’s disease. Cell Mol Life Sci 71(18):3507–3521PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Petkova AT, Leapman RD, Guo Z, Yau W-M, Mattson MP, Tycko R (2005) Self-propagating, molecular-level polymorphism in Alzheimer’s ß-amyloid fibrils. Science 307(5707):262–265PubMedCrossRefGoogle Scholar
  78. 78.
    Fändrich M, Nyström S, Nilsson K, Böckmann A, LeVine H III, Hammarström P (2018) Amyloid fibril polymorphism: a challenge for molecular imaging and therapy. J Intern Med 283(3):218–237PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Mathis CA, Wang Y, Holt DP, Huang G-F, Debnath ML, Klunk WE (2003) Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. J Med Chem 46(13):2740–2754PubMedCrossRefGoogle Scholar
  80. 80.
    Young LJ, Schierle GSK, Kaminski CF (2017) Imaging Aβ (1–42) fibril elongation reveals strongly polarised growth and growth incompetent states. Phys Chem Chem Phys 19(41):27987–27996PubMedCrossRefGoogle Scholar
  81. 81.
    Esler WP, Stimson ER, Jennings JM, Vinters HV, Ghilardi JR, Lee JP, Mantyh PW, Maggio JE (2000) Alzheimer’s disease amyloid propagation by a template-dependent dock-lock mechanism. Biochemistry 39(21):6288–6295PubMedCrossRefGoogle Scholar
  82. 82.
    Schwierz N, Frost CV, Geissler PL, Zacharias M (2016) Dynamics of seeded Aβ40-fibril growth from atomistic molecular dynamics simulations: kinetic trapping and reduced water mobility in the locking step. J Am Chem Soc 138(2):527–539PubMedCrossRefGoogle Scholar
  83. 83.
    Bacci M, Vymětal JÍ, Mihajlovic M, Caflisch A, Vitalis A (2017) Amyloid β fibril elongation by monomers involves disorder at the tip. J Chem Theory Comput 13(10):5117–5130PubMedCrossRefGoogle Scholar
  84. 84.
    Williams TL, Serpell LC (2011) Membrane and surface interactions of Alzheimer’s Aβ peptide–insights into the mechanism of cytotoxicity. FEBS J 278(20):3905–3917PubMedCrossRefGoogle Scholar
  85. 85.
    Kremer JJ, Pallitto MM, Sklansky DJ, Murphy RM (2000) Correlation of β-amyloid aggregate size and hydrophobicity with decreased bilayer fluidity of model membranes. Biochemistry 39(33):10309–10318PubMedCrossRefGoogle Scholar
  86. 86.
    Lindberg DJ, Wesen E, Björkeroth J, Rocha S, Esbjörner EK (2017) Lipid membranes catalyse the fibril formation of the amyloid-β (1–42) peptide through lipid-fibril interactions that reinforce secondary pathways. Biochim et Biophys Acta (BBA)-Biomembr 1859(10):1921–1929CrossRefGoogle Scholar
  87. 87.
    Xiang N, Lyu Y, Zhu X, Narsimhan G (2018) Investigation of the interaction of amyloid β peptide (11–42) oligomers with a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membrane using molecular dynamics simulation. Phys Chem Chem Phys 20(10):6817–6829PubMedCrossRefGoogle Scholar
  88. 88.
    Di Scala C, Yahi N, Boutemeur S, Flores A, Rodriguez L, Chahinian H, Fantini J (2016) Common molecular mechanism of amyloid pore formation by Alzheimer’s β-amyloid peptide and α-synuclein. Sci Rep 6:28781PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Martins IC, Kuperstein I, Wilkinson H, Maes E, Vanbrabant M, Jonckheere W, Van Gelder P, Hartmann D, D’Hooge R, De Strooper B (2008) Lipids revert inert Aβ amyloid fibrils to neurotoxic protofibrils that affect learning in mice. EMBO J 27(1):224–233PubMedCrossRefGoogle Scholar
  90. 90.
    Morales R, Callegari K, Soto C (2015) Prion-like features of misfolded Aβ and tau aggregates. Virus Res 207:106–112PubMedCrossRefGoogle Scholar
  91. 91.
    Stöhr J, Watts JC, Mensinger ZL, Oehler A, Grillo SK, DeArmond SJ, Prusiner SB, Giles K (2012) Purified and synthetic Alzheimer’s amyloid beta (Aβ) prions. Proc Natl Acad Sci 109(27):11025–11030PubMedCrossRefGoogle Scholar
  92. 92.
    Watts JC, Condello C, Stöhr J, Oehler A, Lee J, DeArmond SJ, Lannfelt L, Ingelsson M, Giles K, Prusiner SB (2014) Serial propagation of distinct strains of Aβ prions from Alzheimer’s disease patients. Proc Natl Acad Sci 111(28):10323–10328PubMedCrossRefGoogle Scholar
  93. 93.
    Stroud JC, Liu C, Teng PK, Eisenberg D (2012) Toxic fibrillar oligomers of amyloid-β have cross-β structure. Proc Natl Acad Sci 109(20):7717–7722PubMedCrossRefGoogle Scholar
  94. 94.
    Zhang-Haagen B, Biehl R, Nagel-Steger L, Radulescu A, Richter D, Willbold D (2016) Monomeric amyloid beta peptide in hexafluoroisopropanol detected by small angle neutron scattering. PLoS ONE 11(2):e0150267PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Larson ME, Lesné SE (2012) Soluble Aβ oligomer production and toxicity. J Neurochem 120:125–139PubMedCrossRefGoogle Scholar
  96. 96.
    Wyss-Coray T, Rogers J (2012) Inflammation in Alzheimer disease—a brief review of the basic science and clinical literature. Cold Spring Harb Perspect Med 2(1):a006346PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Ghosh A, Pradhan N, Bera S, Datta A, Krishnamoorthy J, Jana NR, Bhunia A (2017) Inhibition and degradation of amyloid beta (Aβ40) fibrillation by designed small peptide: a combined spectroscopy, microscopy, and cell toxicity study. ACS Chem Neurosci 8(4):718–722PubMedCrossRefGoogle Scholar
  98. 98.
    Caltagirone C, Ferrannini L, Marchionni N, Nappi G, Scapagnini G, Trabucchi M (2012) The potential protective effect of tramiprosate (homotaurine) against Alzheimer’s disease: a review. Aging Clin Exp Res 24(6):580–587PubMedGoogle Scholar
  99. 99.
    Shahzad A (2015) Translational medicine: tools and techniques. Academic Press, LondonGoogle Scholar
  100. 100.
    Martineau E, De Guzman JM, Rodionova L, Kong X, Mayer PM, Aman AM (2010) Investigation of the noncovalent interactions between anti-amyloid agents and amyloid β peptides by ESI-MS. J Am Soc Mass Spectrom 21(9):1506–1514PubMedCrossRefGoogle Scholar
  101. 101.
    Gervais F, Paquette J, Morissette C, Krzywkowski P, Yu M, Azzi M, Lacombe D, Kong X, Aman A, Laurin J (2007) Targeting soluble Aβ peptide with tramiprosate for the treatment of brain amyloidosis. Neurobiol Aging 28(4):537–547CrossRefPubMedGoogle Scholar
  102. 102.
    Watson R (2015) Foods and dietary supplements in the prevention and treatment of disease in older adults. Academic Press, London, p 398Google Scholar
  103. 103.
    Crespi GA, Hermans SJ, Parker MW, Miles LA (2015) Molecular basis for mid-region amyloid-β capture by leading Alzheimer’s disease immunotherapies. Sci Rep 5:9649PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Siemers ER, Friedrich S, Dean RA, Gonzales CR, Farlow MR, Paul SM, DeMattos RB (2010) Safety and changes in plasma and cerebrospinal fluid amyloid β after a single administration of an amyloid β monoclonal antibody in subjects with Alzheimer disease. Clin Neuropharmacol 33(2):67–73PubMedCrossRefGoogle Scholar
  105. 105.
    Farlow M, Arnold SE, Van Dyck CH, Aisen PS, Snider BJ, Porsteinsson AP, Friedrich S, Dean RA, Gonzales C, Sethuraman G (2012) Safety and biomarker effects of solanezumab in patients with Alzheimer’s disease. Alzheimer’s Dement 8(4):261–271CrossRefGoogle Scholar
  106. 106.
    Sacks CA, Avorn J, Kesselheim AS (2017) The failure of Solanezumab-how the Fda saved taxpayers billions. N Engl J Med 376(18):1706–1708PubMedCrossRefGoogle Scholar
  107. 107.
    van Dyck CH (2018) Anti-amyloid-β monoclonal antibodies for Alzheimer’s disease: pitfalls and promise. Biol Psychiat 83(4):311–319PubMedCrossRefGoogle Scholar
  108. 108.
    La Porte SL, Bollini SS, Lanz TA, Abdiche YN, Rusnak AS, Ho W-H, Kobayashi D, Harrabi O, Pappas D, Mina EW (2012) Structural basis of C-terminal β-amyloid peptide binding by the antibody ponezumab for the treatment of Alzheimer’s disease. J Mol Biol 421(4–5):525–536PubMedCrossRefGoogle Scholar
  109. 109.
    Feinberg H, Saldanha JW, Diep L, Goel A, Widom A, Veldman GM, Weis WI, Schenk D, Basi GS (2014) Crystal structure reveals conservation of amyloid-β conformation recognized by 3D6 following humanization to bapineuzumab. Alzheimer’s Res Ther 6(3):31CrossRefGoogle Scholar
  110. 110.
    Miles LA, Crespi GA, Doughty L, Parker MW (2013) Bapineuzumab captures the N-terminus of the Alzheimer’s disease amyloid-beta peptide in a helical conformation. Sci Rep 3:1302PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Vandenberghe R, Rinne JO, Boada M, Katayama S, Scheltens P, Vellas B, Tuchman M, Gass A, Fiebach JB, Hill D (2016) Bapineuzumab for mild to moderate Alzheimer’s disease in two global, randomized, phase 3 trials. Alzheimer’s Res Ther 8(1):18CrossRefGoogle Scholar
  112. 112.
    Tian Y, Zhang X, Li Y, Shoup TM, Teng X, Elmaleh DR, Moore A, Ran C (2014) Crown ethers attenuate aggregation of amyloid beta of Alzheimer’s disease. Chem Commun 50(99):15792–15795CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.College of Health Sciences, Discipline of Pharmaceutical SciencesUniversity of KwaZulu-NatalWestvilleSouth Africa
  2. 2.Department of ChemistryUniversity of LiverpoolLiverpoolUK

Personalised recommendations