The hairpin conformation of the amyloid β peptide is an important structural motif along the aggregation pathway

  • Axel Abelein
  • Jan Pieter Abrahams
  • Jens Danielsson
  • Astrid Gräslund
  • Jüri Jarvet
  • Jinghui Luo
  • Ann Tiiman
  • Sebastian K. T. S. Wärmländer
Part of the following topical collections:
  1. Topical Issue in honor of Ivano Bertini


The amyloid β (Aβ) peptides are 39–42 residue-long peptides found in the senile plaques in the brains of Alzheimer’s disease (AD) patients. These peptides self-aggregate in aqueous solution, going from soluble and mainly unstructured monomers to insoluble ordered fibrils. The aggregation process(es) are strongly influenced by environmental conditions. Several lines of evidence indicate that the neurotoxic species are the intermediate oligomeric states appearing along the aggregation pathways. This minireview summarizes recent findings, mainly based on solution and solid-state NMR experiments and electron microscopy, which investigate the molecular structures and characteristics of the Aβ peptides at different stages along the aggregation pathways. We conclude that a hairpin-like conformation constitutes a common motif for the Aβ peptides in most of the described structures. There are certain variations in different hairpin conformations, for example regarding H-bonding partners, which could be one reason for the molecular heterogeneity observed in the aggregated systems. Interacting hairpins are the building blocks of the insoluble fibrils, again with variations in how hairpins are organized in the cross-section of the fibril, perpendicular to the fibril axis. The secondary structure propensities can be seen already in peptide monomers in solution. Unfortunately, detailed structural information about the intermediate oligomeric states is presently not available. In the review, special attention is given to metal ion interactions, particularly the binding constants and ligand structures of Aβ complexes with Cu(II) and Zn(II), since these ions affect the aggregation process(es) and are considered to be involved in the molecular mechanisms underlying AD pathology.


Alzheimer’s disease Amyloid β peptide Hairpin Protein aggregation Neurotoxicity 



This study was supported by grants from the Swedish Research Council to A.G., from NOW (TOP.08.B3.014) to J.P.A., Estonian Ministry of Education and Research (Targeting Financing Theme SF 9690034s09) to J.J. and from the Magnus Bergvall foundation to S.W. Funding for J.D. was from Swedish Foundation for Strategic Research (MDB10-0030). We thank Dr. Göran Eriksson for fruitful discussions.


  1. 1.
    Haass C, Selkoe DJ (2007) Nat Rev Mol Cell Biol 8:101–112PubMedGoogle Scholar
  2. 2.
    Masters CL, Selkoe DJ (2012) Cold Spring Harb Perspect Med 2:a006262PubMedCentralPubMedGoogle Scholar
  3. 3.
    Sunde M, Blake CC (1998) Q Rev Biophys 31:1–39PubMedGoogle Scholar
  4. 4.
    Eisenberg D, Jucker M (2012) Cell 148:1188–1203PubMedCentralPubMedGoogle Scholar
  5. 5.
    Chiti F, Dobson CM (2006) Annu Rev Biochem 75:333–366PubMedGoogle Scholar
  6. 6.
    Fändrich M (2012) J Mol Biol 421:427–440PubMedGoogle Scholar
  7. 7.
    Selkoe DJ (1991) Neuron 6:487–498PubMedGoogle Scholar
  8. 8.
    Hardy JA, Higgins GA (1992) Science 256:184–185PubMedGoogle Scholar
  9. 9.
    Butterfield SM, Lashuel HA (2010) Angew Chem Int Ed Engl 49:5628–5654PubMedGoogle Scholar
  10. 10.
    Lashuel HA, Hartley D, Petre BM, Walz T, Lansbury PT Jr (2002) Nature 418:291PubMedGoogle Scholar
  11. 11.
    Biancalana M, Koide S (2010) Biochim Biophys Acta 1804:1405–1412PubMedCentralPubMedGoogle Scholar
  12. 12.
    Skeby KK, Sørensen J, Schiøtt B (2013) J Am Chem Soc 135:15114–15128PubMedGoogle Scholar
  13. 13.
    Necula M, Kayed R, Milton S, Glabe CG (2007) J Biol Chem 282:10311–10324PubMedGoogle Scholar
  14. 14.
    Benilova I, Karran E, De Strooper B (2012) Nat Neurosci 15:349–357PubMedGoogle Scholar
  15. 15.
    Nelson R, Sawaya MR, Balbirnie M, Madsen AØ, Riekel C, Grothe R, Eisenberg D (2005) Nature 435:773–778PubMedCentralPubMedGoogle Scholar
  16. 16.
    Sawaya MR, Sambashivan S, Nelson R, Ivanova MI, Sievers SA, Apostol MI, Thompson MJ, Balbirnie M, Wiltzius JJ, McFarlane HT, Madsen AØ, Riekel C, Eisenberg D (2007) Nature 447:453–457PubMedGoogle Scholar
  17. 17.
    Fitzpatrick AW, Debelouchina GT, Bayro MJ, Clare DK, Caporini MA, Bajaj VS, Jaroniec CP, Wang L, Ladizhansky V, Muller SA, MacPhee CE, Waudby CA, Mott HR, De Simone A, Knowles TP, Saibil HR, Vendruscolo M, Orlova EV, Griffin RG, Dobson CM (2013) Proc Natl Acad Sci USA 110:5468–5473PubMedCentralPubMedGoogle Scholar
  18. 18.
    Tycko R (2011) Annu Rev Phys Chem 62:279–299PubMedCentralPubMedGoogle Scholar
  19. 19.
    Wärmländer S, Tiiman A, Abelein A, Luo J, Jarvet J, Söderberg KL, Danielsson J, Gräslund A (2013) ChemBioChem 14:1692–1704PubMedGoogle Scholar
  20. 20.
    Abelein A, Lang L, Lendel C, Gräslund A, Danielsson J (2012) FEBS Lett 586:3991–3995PubMedGoogle Scholar
  21. 21.
    Fawzi NL, Ying J, Torchia DA, Clore GM (2010) J Am Chem Soc 132:9948–9951PubMedCentralPubMedGoogle Scholar
  22. 22.
    Abelein A, Kaspersen JD, Nielsen SB, Jensen GV, Christiansen G, Pedersen JS, Danielsson J, Otzen DE, Gräslund A (2013) J Biol Chem 288:23518–23528PubMedGoogle Scholar
  23. 23.
    Bertini I, Luchinat C, Parigi G, Pierattelli R (2005) ChemBioChem 6:1536–1549PubMedGoogle Scholar
  24. 24.
    Bertini I, Luchinat C, Parigi G, Pierattelli R (2008) Dalton Trans, 3782–3790Google Scholar
  25. 25.
    Bertini I, Gonnelli L, Luchinat C, Mao J, Nesi A (2011) J Am Chem Soc 133:16013–16022PubMedGoogle Scholar
  26. 26.
    De Strooper B, Saftig P, Craessaerts K, Vanderstichele H, Guhde G, Annaert W, Von Figura K, Van Leuven F (1998) Nature 391:387–390PubMedGoogle Scholar
  27. 27.
    Gralle M, Ferreira ST (2007) Prog Neurobiol 82:11–32PubMedGoogle Scholar
  28. 28.
    Barrett PJ, Song Y, Van Horn WD, Hustedt EJ, Schafer JM, Hadziselimovic A, Beel AJ, Sanders CR (2012) Science 336:1168–1171PubMedCentralPubMedGoogle Scholar
  29. 29.
    Riek R, Guntert P, Dobeli H, Wipf B, Wüthrich K (2001) Eur J Biochem 268:5930–5936PubMedGoogle Scholar
  30. 30.
    Shao H, Jao S, Ma K, Zagorski MG (1999) J Mol Biol 285:755–773PubMedGoogle Scholar
  31. 31.
    Jarvet J, Danielsson J, Damberg P, Oleszczuk M, Gräslund A (2007) J Biomol NMR 39:63–72PubMedGoogle Scholar
  32. 32.
    Dyson HJ, Wright PE (2005) Nat Rev Mol Cell Biol 6:197–208PubMedGoogle Scholar
  33. 33.
    Lacy ER, Filippov I, Lewis WS, Otieno S, Xiao L, Weiss S, Hengst L, Kriwacki RW (2004) Nat Struct Mol Biol 11:358–364PubMedGoogle Scholar
  34. 34.
    Danielsson J, Jarvet J, Damberg P, Gräslund A (2002) Magn Reson Chem 40:S89–S97Google Scholar
  35. 35.
    Bernado P, Blackledge M (2009) Biophys J 97:2839–2845PubMedCentralPubMedGoogle Scholar
  36. 36.
    Jarvet J, Damberg P, Danielsson J, Johansson I, Eriksson LE, Gräslund A (2003) FEBS Lett 555:371–374PubMedGoogle Scholar
  37. 37.
    Danielsson J, Jarvet J, Damberg P, Gräslund A (2005) FEBS J 272:3938–3949PubMedGoogle Scholar
  38. 38.
    Danielsson J, Andersson A, Jarvet J, Gräslund A (2006) Magn Reson Chem 44 Spec No:S114–S121Google Scholar
  39. 39.
    Hou L, Shao H, Zhang Y, Li H, Menon NK, Neuhaus EB, Brewer JM, Byeon IJ, Ray DG, Vitek MP, Iwashita T, Makula RA, Przybyla AB, Zagorski MG (2004) J Am Chem Soc 126:1992–2005PubMedGoogle Scholar
  40. 40.
    Yamaguchi T, Matsuzaki K, Hoshino M (2011) FEBS Lett 585:1097–1102PubMedGoogle Scholar
  41. 41.
    Lazo ND, Grant MA, Condron MC, Rigby AC, Teplow DB (2005) Protein Sci 14:1581–1596PubMedCentralPubMedGoogle Scholar
  42. 42.
    Roychaudhuri R, Yang M, Condron MM, Teplow DB (2012) Biochemistry 51:3957–3959PubMedCentralPubMedGoogle Scholar
  43. 43.
    Moriarty DF, Raleigh DP (1999) Biochemistry 38:1811–1818PubMedGoogle Scholar
  44. 44.
    Chiti F, Taddei N, Baroni F, Capanni C, Stefani M, Ramponi G, Dobson CM (2002) Nat Struct Biol 9:137–143PubMedGoogle Scholar
  45. 45.
    Simmons LK, May PC, Tomaselli KJ, Rydel RE, Fuson KS, Brigham EF, Wright S, Lieberburg I, Becker GW, Brems DN et al (1994) Mol Pharmacol 45:373–379PubMedGoogle Scholar
  46. 46.
    Marsh JA, Singh VK, Jia Z, Forman-Kay JD (2006) Protein Sci 15:2795–2804PubMedCentralPubMedGoogle Scholar
  47. 47.
    Tjernberg L, Hosia W, Bark N, Thyberg J, Johansson J (2002) J Biol Chem 277:43243–43246PubMedGoogle Scholar
  48. 48.
    Hoyer W, Grönwall C, Jonsson A, Ståhl S, Härd T (2008) Proc Natl Acad Sci USA 105:5099–5104PubMedCentralPubMedGoogle Scholar
  49. 49.
    Shen Y, Joachimiak A, Rosner MR, Tang WJ (2006) Nature 443:870–874PubMedCentralPubMedGoogle Scholar
  50. 50.
    Lindgren J, Wahlström A, Danielsson J, Markova N, Ekblad C, Gräslund A, Abrahmsén L, Eriksson Karlström A, Wärmländer SKTS (2010) Protein Sci 19:2319–2329PubMedCentralPubMedGoogle Scholar
  51. 51.
    Lindgren J, Segerfeldt P, Sholts SB, Gräslund A, Karlström AE, Wärmländer SK (2013) J Inorg Biochem 120:18–23PubMedGoogle Scholar
  52. 52.
    Sandberg A, Luheshi LM, Söllvander S, Pereira de Barros T, Macao B, Knowles TP, Biverstål H, Lendel C, Ekholm-Petterson F, Dubnovitsky A, Lannfelt L, Dobson CM, Härd T (2010) Proc Natl Acad Sci USA 107:15595–15600PubMedCentralPubMedGoogle Scholar
  53. 53.
    Adlard PA, Bush AI (2006) J Alzheimers Dis 10:145–163PubMedGoogle Scholar
  54. 54.
    Ayton S, Lei P, Bush AI (2013) Free Radic Biol Med 62:76–89PubMedGoogle Scholar
  55. 55.
    Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR (1998) J Neurol Sci 158:47–52PubMedGoogle Scholar
  56. 56.
    Tõugu V, Tiiman A, Palumaa P (2011) Metallomics 3:250–261PubMedGoogle Scholar
  57. 57.
    Tiiman A, Palumaa P, Tõugu V (2013) Neurochem Int 62:367–378PubMedGoogle Scholar
  58. 58.
    Alies B, Renaglia E, Rozga M, Bal W, Faller P, Hureau C (2013) Anal Chem 85:1501–1508PubMedGoogle Scholar
  59. 59.
    Tõugu V, Karafin A, Palumaa P (2008) J Neurochem 104:1249–1259PubMedGoogle Scholar
  60. 60.
    Sacco C, Skowronsky RA, Gade S, Kenney JM, Spuches AM (2012) J Biol Inorg Chem 17:531–541PubMedGoogle Scholar
  61. 61.
    Rozga M, Kloniecki M, Dadlez M, Bal W (2010) Chem Res Toxicol 23:336–340PubMedGoogle Scholar
  62. 62.
    Sarell CJ, Syme CD, Rigby SE, Viles JH (2009) Biochemistry 48:4388–4402PubMedGoogle Scholar
  63. 63.
    Danielsson J, Pierattelli R, Banci L, Gräslund A (2007) FEBS J 274:46–59PubMedGoogle Scholar
  64. 64.
    Badarau A, Dennison C (2011) J Am Chem Soc 133:2983–2988PubMedGoogle Scholar
  65. 65.
    Jeney V, Itoh S, Wendt M, Gradek Q, Ushio-Fukai M, Harrison DG, Fukai T (2005) Circ Res 96:723–729PubMedGoogle Scholar
  66. 66.
    Suzuki K, Miura T, Takeuchi H (2001) Biochem Biophys Res Commun 285:991–996PubMedGoogle Scholar
  67. 67.
    Garai K, Sengupta P, Sahoo B, Maiti S (2006) Biochem Biophys Res Commun 345:210–215PubMedGoogle Scholar
  68. 68.
    Garai K, Sahoo B, Kaushalya SK, Desai R, Maiti S (2007) Biochemistry 46:10655–10663PubMedGoogle Scholar
  69. 69.
    Tõugu V, Karafin A, Zovo K, Chung RS, Howells C, West AK, Palumaa P (2009) J Neurochem 110:1784–1795PubMedGoogle Scholar
  70. 70.
    Pedersen JT, Ostergaard J, Rozlosnik N, Gammelgaard B, Heegaard NH (2011) J Biol Chem 286:26952–26963PubMedCentralPubMedGoogle Scholar
  71. 71.
    Yoshiike Y, Tanemura K, Murayama O, Akagi T, Murayama M, Sato S, Sun X, Tanaka N, Takashima A (2001) J Biol Chem 276:32293–32299PubMedGoogle Scholar
  72. 72.
    Ghalebani L, Wahlström A, Danielsson J, Wärmländer SK, Gräslund A (2012) Biochem Biophys Res Commun 421:554–560PubMedGoogle Scholar
  73. 73.
    Huang X, Atwood CS, Hartshorn MA, Multhaup G, Goldstein LE, Scarpa RC, Cuajungco MP, Gray DN, Lim J, Moir RD, Tanzi RE, Bush AI (1999) Biochemistry 38:7609–7616PubMedGoogle Scholar
  74. 74.
    Cardoso SM, Rego AC, Pereira C, Oliveira CR (2005) Neurotox Res 7:273–281PubMedGoogle Scholar
  75. 75.
    Johansson AS, Vestling M, Zetterström P, Lang L, Leinartaite L, Karlström M, Danielsson J, Marklund SL, Oliveberg M (2012) PLoS ONE 7:e36104PubMedCentralPubMedGoogle Scholar
  76. 76.
    Minicozzi V, Stellato F, Comai M, Dalla Serra M, Potrich C, Meyer-Klaucke W, Morante S (2008) J Biol Chem 283:10784–10792PubMedGoogle Scholar
  77. 77.
    Zirah S, Kozin SA, Mazur AK, Blond A, Cheminant M, Segalas-Milazzo I, Debey P, Rebuffat S (2006) J Biol Chem 281:2151–2161PubMedGoogle Scholar
  78. 78.
    Drew SC, Noble CJ, Masters CL, Hanson GR, Barnham KJ (2009) J Am Chem Soc 131:1195–1207PubMedGoogle Scholar
  79. 79.
    Gaggelli E, Janicka-Klos A, Jankowska E, Kozlowski H, Migliorini C, Molteni E, Valensin D, Valensin G, Wieczerzak E (2008) J Phys Chem B 112:100–109PubMedGoogle Scholar
  80. 80.
    Hureau C, Coppel Y, Dorlet P, Solari PL, Sayen S, Guillon E, Sabater L, Faller P (2009) Angew Chem 48:9522–9525Google Scholar
  81. 81.
    Zirah S, Rebuffat S, Kozin SA, Debey P, Fournier F, Lesage D, Tabet JC (2003) Int J Mass Spectrom 228:999–1016Google Scholar
  82. 82.
    Valiente-Gabioud AA, Torres-Monserrat V, Molina-Rubino L, Binolfi A, Griesinger C, Fernandez CO (2012) J Inorg Biochem 117:334–341PubMedGoogle Scholar
  83. 83.
    Rezaei-Ghaleh N, Giller K, Becker S, Zweckstetter M (2011) Biophys J 101:1202–1211PubMedCentralPubMedGoogle Scholar
  84. 84.
    Yang DS, McLaurin J, Qin K, Westaway D, Fraser PE (2000) Eur J Biochem 267:6692–6698PubMedGoogle Scholar
  85. 85.
    Miura T, Suzuki K, Takeuchi H (2001) J Mol Struct 598:79–84Google Scholar
  86. 86.
    Curtain CC, Ali F, Volitakis I, Cherny RA, Norton RS, Beyreuther K, Barrow CJ, Masters CL, Bush AI, Barnham KJ (2001) J Biol Chem 276:20466–20473PubMedGoogle Scholar
  87. 87.
    Miura T, Suzuki K, Kohata N, Takeuchi H (2000) Biochemistry 39:7024–7031PubMedGoogle Scholar
  88. 88.
    Heise H (2008) ChemBioChem 9:179–189PubMedGoogle Scholar
  89. 89.
    Paravastu AK, Qahwash I, Leapman RD, Meredith SC, Tycko R (2009) Proc Natl Acad Sci USA 106:7443–7448PubMedCentralPubMedGoogle Scholar
  90. 90.
    Spencer RG, Halverson KJ, Auger M, McDermott AE, Griffin RG, Lansbury PT Jr (1991) Biochemistry 30:10382–10387PubMedGoogle Scholar
  91. 91.
    Lansbury PT Jr, Costa PR, Griffiths JM, Simon EJ, Auger M, Halverson KJ, Kocisko DA, Hendsch ZS, Ashburn TT, Spencer RG et al (1995) Nat Struct Biol 2:990–998PubMedGoogle Scholar
  92. 92.
    Costa PR, Kocisko DA, Sun BQ, Lansbury PT Jr, Griffin RG (1997) J Am Chem Soc 119:10487–10493Google Scholar
  93. 93.
    Antzutkin ON, Balbach JJ, Leapman RD, Rizzo NW, Reed J, Tycko R (2000) Proc Natl Acad Sci USA 97:13045–13050PubMedCentralPubMedGoogle Scholar
  94. 94.
    Benzinger TL, Gregory DM, Burkoth TS, Miller-Auer H, Lynn DG, Botto RE, Meredith SC (1998) Proc Natl Acad Sci USA 95:13407–13412PubMedCentralPubMedGoogle Scholar
  95. 95.
    Lührs T, Ritter C, Adrian M, Riek-Loher D, Bohrmann B, Döbeli H, Schubert D, Riek R (2005) Proc Natl Acad Sci USA 102:17342–17347PubMedCentralPubMedGoogle Scholar
  96. 96.
    Luo J, Otero JM, Yu CH, Wärmländer SK, Gräslund A, Overhand M, Abrahams JP (2013) Chemistry 19:17338–17348PubMedGoogle Scholar
  97. 97.
    Qiang W, Yau WM, Luo Y, Mattson MP, Tycko R (2012) Proc Natl Acad Sci USA 109:4443–4448PubMedCentralPubMedGoogle Scholar
  98. 98.
    Lu JX, Qiang W, Yau WM, Schwieters CD, Meredith SC, Tycko R (2013) Cell 154:1257–1268PubMedGoogle Scholar
  99. 99.
    Safar J, Wille H, Itri V, Groth D, Serban H, Torchia M, Cohen FE, Prusiner SB (1998) Nat Med 4:1157–1165PubMedGoogle Scholar
  100. 100.
    Stohr J, Watts JC, Mensinger ZL, Oehler A, Grillo SK, DeArmond SJ, Prusiner SB, Giles K (2012) Proc Natl Acad Sci USA 109:11025–11030PubMedCentralPubMedGoogle Scholar
  101. 101.
    Bertini I, Gallo G, Korsak M, Luchinat C, Mao J, Ravera E (2013) ChemBioChem 14:1891–1897PubMedGoogle Scholar
  102. 102.
    Parthasarathy S, Long F, Miller Y, Xiao Y, McElheny D, Thurber K, Ma B, Nussinov R, Ishii Y (2011) J Am Chem Soc 133:3390–3400PubMedCentralPubMedGoogle Scholar
  103. 103.
    Grigorieff N, Harrison SC (2011) Curr Opin Struct Biol 21:265–273PubMedCentralPubMedGoogle Scholar
  104. 104.
    Nederlof I, Li YW, van Heel M, Abrahams JP (2013) Acta Crystallogr Sect D Biol Crystallogr 69:852–859Google Scholar
  105. 105.
    Sachse C, Xu C, Wieligmann K, Diekmann S, Grigorieff N, Fändrich M (2006) J Mol Biol 362:347–354PubMedGoogle Scholar
  106. 106.
    Sachse C, Fändrich M, Grigorieff N (2008) Proc Natl Acad Sci USA 105:7462–7466PubMedCentralPubMedGoogle Scholar
  107. 107.
    Sachse C, Grigorieff N, Fändrich M (2010) Angew Chem Int Ed Engl 49:1321–1323PubMedCentralPubMedGoogle Scholar
  108. 108.
    Zhang R, Hu X, Khant H, Ludtke SJ, Chiu W, Schmid MF, Frieden C, Lee JM (2009) Proc Natl Acad Sci USA 106:4653–4658PubMedCentralPubMedGoogle Scholar
  109. 109.
    Miller Y, Ma B, Tsai CJ, Nussinov R (2010) Proc Natl Acad Sci USA 107:14128–14133PubMedCentralPubMedGoogle Scholar
  110. 110.
    Schmidt M, Sachse C, Richter W, Xu C, Fändrich M, Grigorieff N (2009) Proc Natl Acad Sci USA 106:19813–19818PubMedCentralPubMedGoogle Scholar
  111. 111.
    Bodner CR, Dobson CM, Bax A (2009) J Mol Biol 390:775–790PubMedCentralPubMedGoogle Scholar
  112. 112.
    Hallbeck M, Nath S, Marcusson J (2013) Neuroscientist 19:560–566PubMedGoogle Scholar
  113. 113.
    Matlack KE, Tardiff DF, Narayan P, Hamamichi S, Caldwell KA, Caldwell GA, Lindquist S (2014) Proc Natl Acad Sci USA 111:4013–4018PubMedCentralPubMedGoogle Scholar
  114. 114.
    Petkova AT, Yau WM, Tycko R (2006) Biochemistry 45:498–512PubMedCentralPubMedGoogle Scholar
  115. 115.
    Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) J Comput Chem 25:1605–1612PubMedGoogle Scholar

Copyright information

© SBIC 2014

Authors and Affiliations

  • Axel Abelein
    • 1
  • Jan Pieter Abrahams
    • 2
  • Jens Danielsson
    • 1
  • Astrid Gräslund
    • 1
  • Jüri Jarvet
    • 1
    • 3
  • Jinghui Luo
    • 2
  • Ann Tiiman
    • 1
  • Sebastian K. T. S. Wärmländer
    • 1
  1. 1.Department of Biochemistry and Biophysics, Arrhenius LaboratoriesStockholm UniversityStockholmSweden
  2. 2.Gorlaeus Laboratory, Leiden Institute of ChemistryLeiden UniversityLeidenThe Netherlands
  3. 3.The National Institute of Chemical Physics and BiophysicsTallinnEstonia

Personalised recommendations