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Nanoprobing of the Effect of Cu2+ Cations on Misfolding, Interaction and Aggregation of Amyloid β Peptide

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Abstract

Misfolding and aggregation of the amyloid β-protein (Aβ) are hallmarks of Alzheimer’s disease. Both processes are dependent on the environmental conditions, including the presence of divalent cations, such as Cu2+. Cu2+ cations regulate early stages of Aβ aggregation, but the molecular mechanism of Cu2+ regulation is unknown. In this study we applied single molecule AFM force spectroscopy to elucidate the role of Cu2+ cations on interpeptide interactions. By immobilizing one of two interacting Aβ42 molecules on a mica surface and tethering the counterpart molecule onto the tip, we were able to probe the interpeptide interactions in the presence and absence of Cu2+ cations at pH 7.4, 6.8, 6.0, 5.0, and 4.0. The results show that the presence of Cu2+ cations change the pattern of Aβ interactions for pH values between pH 7.4 and pH 5.0. Under these conditions, Cu2+ cations induce Aβ42 peptide structural changes resulting in N-termini interactions within the dimers. Cu2+ cations also stabilize the dimers. No effects of Cu2+ cations on Aβ-Aβ interactions were observed at pH 4.0, suggesting that peptide protonation changes the peptide-cation interaction. The effect of Cu2+ cations on later stages of Aβ aggregation was studied by AFM topographic images. The results demonstrate that substoichiometric Cu2+ cations accelerate the formation of fibrils at pH 7.4 and 5.0, whereas no effect of Cu2+ cations was observed at pH 4.0. Taken together, the combined AFM force spectroscopy and imaging analyses demonstrate that Cu2+ cations promote both the initial and the elongation stages of Aβ aggregation, but protein protonation diminishes the effect of Cu2+.

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References

  • Ahmed M, Davis J, Aucoin D, Sato T, Ahuja S, Aimoto S, Elliott JI, Van Nostrand WE, Smith SO (2010) Structural conversion of neurotoxic amyloid-beta(1-42) oligomers to fibrils. Nat Struct Mol Biol 17(5):561–567. doi:10.1038/nsmb.1799

    Article  PubMed  CAS  Google Scholar 

  • Ali-Torres J, Rodriguez-Santiago L, Sodupe M (2011) Computational calculations of pKa values of imidazole in Cu(II) complexes of biological relevance. Phys Chem Chem Phys 13(17):7852–7861. doi:10.1039/c0cp02319a

    Article  PubMed  CAS  Google Scholar 

  • Atwood CS, Moir RD, Huang X, Scarpa RC, Bacarra NM, Romano DM, Hartshorn MA, Tanzi RE, Bush AI (1998) Dramatic aggregation of Alzheimer abeta by Cu(II) is induced by conditions representing physiological acidosis. J Biol Chem 273(21):12817–12826. doi:10.1074/jbc.273.21.12817

    Article  PubMed  CAS  Google Scholar 

  • Barnham KJ, Masters CL, Bush AI (2004) Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov 3(3):205–214. doi:10.1038/nrd1330

    Article  PubMed  CAS  Google Scholar 

  • Beyer MK, Clausen-Schaumann H (2005) Mechanochemistry: the mechanical activation of covalent bonds. Chem Rev 105(8):2921–2948. doi:10.1021/cr030697h

    Article  PubMed  CAS  Google Scholar 

  • Bitan G, Kirkitadze MD, Lomakin A, Vollers SS, Benedek GB, Teplow DB (2003) Amyloid beta -protein (Abeta) assembly: Abeta 40 and Abeta 42 oligomerize through distinct pathways. Proc Natl Acad Sci U S A 100(1):330–335. doi:10.1073/pnas.222681699

    Article  PubMed  CAS  Google Scholar 

  • Bush AI, Tanzi RE (2008) Therapeutics for Alzheimer’s disease based on the metal hypothesis. Neurotherapeutics 5(3):421–432. doi:10.1016/j.nurt.2008.05.001

    Article  PubMed  CAS  Google Scholar 

  • Chen WT, Liao YH, Yu HM, Cheng IH, Chen YR (2011) Distinct effects of Zn2+, Cu2+, Fe3+, and Al3+ on amyloid-beta stability, oligomerization, and aggregation: amyloid-beta destabilization promotes annular protofibril formation. J Biol Chem 286(11):9646–9656. doi:10.1074/jbc.M110.177246

    Article  PubMed  CAS  Google Scholar 

  • Dobson CM (2003) Protein folding and misfolding. Nature 426(6968):884–890. doi:10.1038/nature02261

    Article  PubMed  CAS  Google Scholar 

  • Dong J, Canfield JM, Mehta AK, Shokes JE, Tian B, Childers WS, Simmons JA, Mao Z, Scott RA, Warncke K, Lynn DG (2007) Engineering metal ion coordination to regulate amyloid fibril assembly and toxicity. Proc Natl Acad Sci U S A 104(33):13313–13318. doi:10.1073/pnas.0702669104

    Article  PubMed  CAS  Google Scholar 

  • Drew SC, Masters CL, Barnham KJ (2009) Alanine-2 carbonyl is an oxygen ligand in Cu2+ coordination of Alzheimer’s disease amyloid-beta peptide–relevance to N-terminally truncated forms. J Am Chem Soc 131(25):8760–8761. doi:10.1021/ja903669a

    Article  PubMed  CAS  Google Scholar 

  • Faller P (2009) Copper and zinc binding to amyloid-beta: coordination, dynamics, aggregation, reactivity and metal-ion transfer. ChemBioChem 10(18):2837–2845. doi:10.1002/cbic.200900321

    Article  PubMed  CAS  Google Scholar 

  • Faller EM, Brown DL (2009) Modulation of microtubule dynamics by the microtubule-associated protein 1a. J Neurosci Res 87(5):1080–1089. doi:10.1002/jnr.21920

    Article  PubMed  CAS  Google Scholar 

  • Fezoui Y, Teplow DB (2002) Kinetic studies of amyloid beta-protein fibril assembly. Differential effects of alpha-helix stabilization. J Biol Chem 277(40):36948–36954. doi:10.1074/jbc.M204168200

    Article  PubMed  CAS  Google Scholar 

  • Gomez-Casado A, Dam HH, Yilmaz MD, Florea D, Jonkheijm P, Huskens J (2011) Probing multivalent interactions in a synthetic host-guest complex by dynamic force spectroscopy. J Am Chem Soc 133(28):10849–10857. doi:10.1021/ja2016125

    Article  PubMed  CAS  Google Scholar 

  • Haupt C, Leppert J, Ronicke R, Meinhardt J, Yadav JK, Ramachandran R, Ohlenschlager O, Reymann KG, Gorlach M, Fandrich M (2012) Structural basis of beta-amyloid-dependent synaptic dysfunctions. Angew Chem Int Ed Engl 51(7):1576–1579. doi:10.1002/anie.201105638

    Article  PubMed  CAS  Google Scholar 

  • Hong L, Simon JD (2011) Insights into the thermodynamics of copper association with amyloid-beta, alpha-synuclein and prion proteins. Metallomics 3(3):262–266. doi:10.1039/c0mt00052c

    Article  PubMed  CAS  Google Scholar 

  • Hong L, Carducci TM, Bush WD, Dudzik CG, Millhauser GL, Simon JD (2010) Quantification of the binding properties of Cu2+ to the amyloid beta peptide: coordination spheres for human and rat peptides and implication on Cu2 + -induced aggregation. J Phys Chem B 114(34):11261–11271. doi:10.1021/jp103272v

    Article  PubMed  CAS  Google Scholar 

  • Huang X, Atwood CS, Moir RD, Hartshorn MA, Tanzi RE, Bush AI (2004) Trace metal contamination initiates the apparent auto-aggregation, amyloidosis, and oligomerization of Alzheimer’s Abeta peptides. J Biol Inorg Chem 9(8):954–960. doi:10.1007/s00775-004-0602-8

    Article  PubMed  CAS  Google Scholar 

  • Hung YH, Bush AI, Cherny RA (2010) Copper in the brain and Alzheimer’s disease. J Biol Inorg Chem 15(1):61–76. doi:10.1007/s00775-009-0600-y

    Article  PubMed  CAS  Google Scholar 

  • Innocenti M, Salvietti E, Guidotti M, Casini A, Bellandi S, Foresti ML, Gabbiani C, Pozzi A, Zatta P, Messori L (2010) Trace copper(II) or zinc(II) ions drastically modify the aggregation behavior of amyloid-beta1-42: an AFM study. J Alzheimers Dis 19(4):1323–1329. doi:10.3233/JAD-2010-1338

    PubMed  CAS  Google Scholar 

  • Jomova K, Vondrakova D, Lawson M, Valko M (2010) Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem 345(1–2):91–104. doi:10.1007/s11010-010-0563-x

    Article  PubMed  CAS  Google Scholar 

  • Jones OG, Mezzenga R (2012) Inhibiting, promoting, and preserving stability of functional protein fibrils. Soft Matter 8(4):876–895. doi:10.1039/C1SM06643A

    Article  CAS  Google Scholar 

  • Kenche VB, Barnham KJ (2011) Alzheimer’s disease & metals: therapeutic opportunities. Br J Pharmacol 163(2):211–219. doi:10.1111/j.1476-5381.2011.01221.x

    Article  PubMed  CAS  Google Scholar 

  • Kim BH, Palermo NY, Lovas S, Zaikova T, Keana JF, Lyubchenko YL (2011) Single-molecule atomic force microscopy force spectroscopy study of Abeta-40 interactions. Biochemistry 50(23):5154–5162. doi:10.1021/bi200147a

    Article  PubMed  CAS  Google Scholar 

  • Kirkitadze MD, Condron MM, Teplow DB (2001) Identification and characterization of key kinetic intermediates in amyloid beta-protein fibrillogenesis. J Mol Biol 312(5):1103–1119. doi:10.1006/jmbi.2001.4970

    Article  PubMed  CAS  Google Scholar 

  • Klug GM, Losic D, Subasinghe SS, Aguilar MI, Martin LL, Small DH (2003) Beta-amyloid protein oligomers induced by metal ions and acid pH are distinct from those generated by slow spontaneous ageing at neutral pH. Eur J Biochem 270(21):4282–4293. doi:10.1046/j.1432-1033.2003.03815.x

    Article  PubMed  CAS  Google Scholar 

  • Krasnoslobodtsev AV, Shlyakhtenko LS, Lyubchenko YL (2007) Probing Interactions within the synaptic DNA-SfiI complex by AFM force spectroscopy. J Mol Biol 365(5):1407–1416. doi:10.1016/j.jmb.2006.10.041

    Article  PubMed  CAS  Google Scholar 

  • Lazo ND, Grant MA, Condron MC, Rigby AC, Teplow DB (2005) On the nucleation of amyloid beta-protein monomer folding. Protein Sci 14(6):1581–1596. doi:10.1110/ps.041292205

    Article  PubMed  CAS  Google Scholar 

  • Lin CJ, Huang HC, Jiang ZF (2010) Cu(II) interaction with amyloid-beta peptide: a review of neuroactive mechanisms in AD brains. Brain Res Bull 82(5–6):235–242. doi:10.1016/j.brainresbull.2010.06.003

    Article  PubMed  CAS  Google Scholar 

  • Lyubchenko YL, Kim BH, Krasnoslobodtsev AV, Yu J (2010) Nanoimaging for protein misfolding diseases. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2(5):526–543. doi:10.1002/wnan.102

    Article  PubMed  CAS  Google Scholar 

  • Masters CL, Selkoe DJ (2012) Biochemistry of amyloid β-protein and amyloid deposits in Alzheimer disease. Cold Spring Harb Perspect Med. doi:10.1101/cshperspect.a006262

  • Miura T, Suzuki K, Kohata N, Takeuchi H (2000) Metal binding modes of Alzheimer’s amyloid beta-peptide in insoluble aggregates and soluble complexes. Biochemistry 39(23):7024–7031. doi:10.1021/bi0002479

    Article  PubMed  CAS  Google Scholar 

  • Miura T, Mitani S, Takanashi C, Mochizuki N (2004) Copper selectively triggers beta-sheet assembly of an N-terminally truncated amyloid beta-peptide beginning with Glu3. J Inorg Biochem 98(1):10–14. doi:10.1016/j.jinorgbio.2003.10.008

    Article  PubMed  CAS  Google Scholar 

  • Murakami K, Irie K, Ohigashi H, Hara H, Nagao M, Shimizu T, Shirasawa T (2005) Formation and stabilization model of the 42-mer Abeta radical: implications for the long-lasting oxidative stress in Alzheimer’s disease. J Am Chem Soc 127(43):15168–15174. doi:10.1021/ja054041c

    Article  PubMed  CAS  Google Scholar 

  • Murariu M, Dragan ES, Drochioiu G (2007) Synthesis and mass spectrometric characterization of a metal-affinity decapeptide: copper-induced conformational changes. Biomacromolecules 8(12):3836–3841. doi:10.1021/bm700793g

    Article  PubMed  CAS  Google Scholar 

  • Olofsson A, Lindhagen-Persson M, Vestling M, Sauer-Eriksson AE, Öhman A (2009) Quenched hydrogen/deuterium exchange NMR characterization of amyloid-β peptide aggregates formed in the presence of Cu2+ or Zn2+. FEBS J 276(15):4051–4060. doi:10.1111/j.1742-4658.2009.07113.x

    Article  PubMed  CAS  Google Scholar 

  • Olubiyi OO, Strodel B (2012) Structures of the amyloid beta-peptides Abeta1-40 and Abeta1-42 as influenced by pH and a D-peptide. J Phys Chem B 116(10):3280–3291. doi:10.1021/jp2076337

    Article  PubMed  CAS  Google Scholar 

  • Ono K, Condron MM, Teplow DB (2009) Structure-neurotoxicity relationships of amyloid beta-protein oligomers. Proc Natl Acad Sci U S A 106(35):14745–14750. doi:10.1073/pnas.0905127106

    Article  PubMed  CAS  Google Scholar 

  • Parthasarathy S, Long F, Miller Y, Xiao Y, McElheny D, Thurber K, Ma B, Nussinov R, Ishii Y (2011) Molecular-level examination of Cu2+ binding structure for amyloid fibrils of 40-residue Alzheimer’s beta by solid-state NMR spectroscopy. J Am Chem Soc 133(10):3390–3400. doi:10.1021/ja1072178

    Article  PubMed  CAS  Google Scholar 

  • Portillo AM, Krasnoslobodtsev AV, Lyubchenko YL (2012) Effect of electrostatics on aggregation of prion protein Sup35 peptide. J Phys Condens Matter 24(16):164205. doi:10.1088/0953-8984/24/16/164205

    Article  PubMed  Google Scholar 

  • Rauk A (2009) The chemistry of Alzheimer’s disease. Chem Soc Rev 38(9):2698–2715. doi:10.1039/b807980n

    Article  PubMed  CAS  Google Scholar 

  • Rivera-Mancia S, Perez-Neri I, Rios C, Tristan-Lopez L, Rivera-Espinosa L, Montes S (2010) The transition metals copper and iron in neurodegenerative diseases. Chem Biol Interact 186(2):184–199. doi:10.1016/j.cbi.2010.04.010

    Article  PubMed  CAS  Google Scholar 

  • Roberts BR, Ryan TM, Bush AI, Masters CL, Duce JA (2012) The role of metallobiology and amyloid-beta peptides in Alzheimer’s disease. J Neurochem 120(Suppl 1):149–166. doi:10.1111/j.1471-4159.2011.07500.x

    Article  PubMed  CAS  Google Scholar 

  • Sarell CJ, Syme CD, Rigby SE, Viles JH (2009) Copper(II) binding to amyloid-beta fibrils of Alzheimer’s disease reveals a picomolar affinity: stoichiometry and coordination geometry are independent of Abeta oligomeric form. Biochemistry 48(20):4388–4402. doi:10.1021/bi900254n

    Article  PubMed  CAS  Google Scholar 

  • Sarell CJ, Wilkinson SR, Viles JH (2010) Substoichiometric levels of Cu2+ ions accelerate the kinetics of fiber formation and promote cell toxicity of amyloid-{beta} from Alzheimer disease. J Biol Chem 285(53):41533–41540. doi:10.1074/jbc.M110.171355

    Article  PubMed  CAS  Google Scholar 

  • Schmitt L, Ludwig M, Gaub HE, Tampe R (2000) A metal-chelating microscopy tip as a new toolbox for single-molecule experiments by atomic force microscopy. Biophys J 78(6):3275–3285. doi:10.1016/S0006-3495(00)76863-9

    Article  PubMed  CAS  Google Scholar 

  • Shin BK, Saxena S (2008) Direct evidence that all three histidine residues coordinate to Cu(II) in amyloid-beta1-16. Biochemistry 47(35):9117–9123. doi:10.1021/bi801014x

    Article  PubMed  CAS  Google Scholar 

  • Smith DP, Smith DG, Curtain CC, Boas JF, Pilbrow JR, Ciccotosto GD, Lau TL, Tew DJ, Perez K, Wade JD, Bush AI, Drew SC, Separovic F, Masters CL, Cappai R, Barnham KJ (2006) Copper-mediated amyloid-beta toxicity is associated with an intermolecular histidine bridge. J Biol Chem 281(22):15145–15154. doi:10.1074/jbc.M600417200

    Article  PubMed  CAS  Google Scholar 

  • Smith DP, Ciccotosto GD, Tew DJ, Fodero-Tavoletti MT, Johanssen T, Masters CL, Barnham KJ, Cappai R (2007) Concentration dependent Cu2+ induced aggregation and dityrosine formation of the Alzheimer’s disease amyloid-beta peptide. Biochemistry 46(10):2881–2891. doi:10.1021/bi0620961

    Article  PubMed  CAS  Google Scholar 

  • Snyder SW, Ladror US, Wade WS, Wang GT, Barrett LW, Matayoshi ED, Huffaker HJ, Krafft GA, Holzman TF (1994) Amyloid-beta aggregation: selective inhibition of aggregation in mixtures of amyloid with different chain lengths. Biophys J 67(3):1216–1228. doi:10.1016/S0006-3495(94)80591-0

    Article  PubMed  CAS  Google Scholar 

  • Sparks DL, Schreurs BG (2003) Trace amounts of copper in water induce beta-amyloid plaques and learning deficits in a rabbit model of Alzheimer’s disease. Proc Natl Acad Sci U S A 100(19):11065–11069. doi:10.1073/pnas.1832769100

    Article  PubMed  CAS  Google Scholar 

  • Stellato F, Menestrina G, Serra MD, Potrich C, Tomazzolli R, Meyer-Klaucke W, Morante S (2006) Metal binding in amyloid beta-peptides shows intra- and inter-peptide coordination modes. Eur Biophys J 35(4):340–351. doi:10.1007/s00249-005-0041-7

    Article  PubMed  CAS  Google Scholar 

  • Streltsov VA, Titmuss SJ, Epa VC, Barnham KJ, Masters CL, Varghese JN (2008) The structure of the amyloid-beta peptide high-affinity copper II binding site in Alzheimer disease. Biophys J 95(7):3447–3456. doi:10.1529/biophysj.108.134429

    Article  PubMed  CAS  Google Scholar 

  • Stroud JC, Liu C, Teng PK, Eisenberg D (2012) Toxic fibrillar oligomers of amyloid-beta have cross-beta structure. Proc Natl Acad Sci U S A. doi:10.1073/pnas.1203193109

  • Sulchek TA, Friddle RW, Langry K, Lau EY, Albrecht H, Ratto TV, DeNardo SJ, Colvin ME, Noy A (2005) Dynamic force spectroscopy of parallel individual Mucin1-antibody bonds. Proc Natl Acad Sci U S A 102(46):16638–16643. doi:10.1073/pnas.0505208102

    Article  PubMed  CAS  Google Scholar 

  • Syme CD, Nadal RC, Rigby SE, Viles JH (2004) Copper binding to the amyloid-beta (Abeta) peptide associated with Alzheimer’s disease: folding, coordination geometry, pH dependence, stoichiometry, and affinity of Abeta-(1-28): insights from a range of complementary spectroscopic techniques. J Biol Chem 279(18):18169–18177. doi:10.1074/jbc.M313572200

    Article  PubMed  CAS  Google Scholar 

  • Tougu V, Tiiman A, Palumaa P (2011) Interactions of Zn(II) and Cu(II) ions with Alzheimer’s amyloid-beta peptide. Metal ion binding, contribution to fibrillization and toxicity. Metallomics 3(3):250–261. doi:10.1039/c0mt00073f

    Article  PubMed  CAS  Google Scholar 

  • Walsh DM, Lomakin A, Benedek GB, Condron MM, Teplow DB (1997) Amyloid beta-protein fibrillogenesis. Detection of a protofibrillar intermediate. J Biol Chem 272(35):22364–22372. doi:10.1074/jbc.272.35.22364

    Article  PubMed  CAS  Google Scholar 

  • Yang H, Pritzker M, Fung SY, Sheng Y, Wang W, Chen P (2006) Anion effect on the nanostructure of a metal ion binding self-assembling peptide. Langmuir 22(20):8553–8562. doi:10.1021/la061238p

    Article  PubMed  CAS  Google Scholar 

  • Yu J, Lyubchenko YL (2009) Early stages for Parkinson’s development: alpha-synuclein misfolding and aggregation. J Neuroimmune Pharm 4(1):10–16. doi:10.1007/s11481-008-9115-5

    Article  Google Scholar 

  • Yu J, Malkova S, Lyubchenko YL (2008) alpha-Synuclein misfolding: single molecule AFM force spectroscopy study. J Mol Biol 384(4):992–1001. doi:10.1016/j.jmb.2008.10.006

    Article  PubMed  CAS  Google Scholar 

  • Yu J, Warnke J, Lyubchenko YL (2011) Nanoprobing of alpha-synuclein misfolding and aggregation with atomic force microscopy. Nanomedicine 7(2):146–152. doi:10.1016/j.nano.2010.08.001

    Article  PubMed  CAS  Google Scholar 

  • Zou J, Kajita K, Sugimoto N (2001) Cu(2+) inhibits the aggregation of amyloid beta-peptide(1-42) in vitro. Angew Chem Int Ed Engl 40(12):2274–2277. doi:10.1002/1521-3773(20010618)40:12<2274::AID-ANIE2274>3.0.CO;2-5

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank A. Krasnoslobodtsev, A. Portillo, Zenghan Tong, Yuliang Zhang and other group members for insightful suggestions and discussions. The work was supported by grants to Y.L.L. from the National Institutes of Health (NIH: GM096039), U.S. Department of Energy Grant DE-FG02-08ER64579, the Nebraska Research Initiative and grants to D.B.T. from NIH (NS038328, AG041295) and the Jim Easton Consortium for Drug Development and Biomarkers.

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The estimation of contour length of all tethers; the force spectroscopy results in the presence and absence of Cu2+ cations at pH 6.8 and 6.0. This material is available free of charge via the Internet

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, 68198, USA

    Zhengjian Lv & Yuri L. Lyubchenko

  2. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA

    Margaret M. Condron & David B. Teplow

  3. Molecular Biology and Brain Research Institutes, and Mary S. Easton Center for Alzheimer’s Disease Research at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA

    David B. Teplow

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  1. Zhengjian Lv
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Correspondence to Yuri L. Lyubchenko.

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The estimation of contour length of all tethers; the force spectroscopy results in the presence and absence of Cu2+ cations at pH 6.8 and 6.0. This material is available free of charge via the Internet. (DOC 4609 kb)

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Lv, Z., Condron, M.M., Teplow, D.B. et al. Nanoprobing of the Effect of Cu2+ Cations on Misfolding, Interaction and Aggregation of Amyloid β Peptide. J Neuroimmune Pharmacol 8, 262–273 (2013). https://doi.org/10.1007/s11481-012-9416-6

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