Neurobiology of Aging
Volume 30, Issue 7 , Pages 1069-1077 , July 2009

Zinc and copper modulate Alzheimer Aβ levels in human cerebrospinal fluid

  • Dorothea Strozyk

      Affiliations

    • Albert Einstein College of Medicine, Department of Neurology, Bronx, NY, United States
    • Laboratory of Epidemiology, Demography and Biometry, Neuroepidemiology Section, National Institute on Aging, NIH, Bethesda, MD 20892, United States
    • ,
  • Lenore J. Launer

      Affiliations

    • Laboratory of Epidemiology, Demography and Biometry, Neuroepidemiology Section, National Institute on Aging, NIH, Bethesda, MD 20892, United States
    • Corresponding Author InformationCorresponding author. Tel.: +1 301 496 6214, fax: +1 301 496 4006.
    • ,
  • Paul A. Adlard

      Affiliations

    • Mental Health Research Institute of Victoria, Department of Pathology, The University of Melbourne, Australia
    • ,
  • Robert A. Cherny

      Affiliations

    • Mental Health Research Institute of Victoria, Department of Pathology, The University of Melbourne, Australia
    • ,
  • Andrew Tsatsanis

      Affiliations

    • Mental Health Research Institute of Victoria, Department of Pathology, The University of Melbourne, Australia
    • ,
  • Irene Volitakis

      Affiliations

    • Mental Health Research Institute of Victoria, Department of Pathology, The University of Melbourne, Australia
    • ,
  • Kaj Blennow

      Affiliations

    • Department of Clinical Neuroscience, Sahlgren's University Hospital, Moelndal, Sweden
    • ,
  • Helen Petrovitch

      Affiliations

    • Kuakini Medical Center, Pacific Health Research Institute, Honolulu, HI, United States
    • ,
  • Lon R. White

      Affiliations

    • Kuakini Medical Center, Pacific Health Research Institute, Honolulu, HI, United States
    • ,
  • Ashley I. Bush

      Affiliations

    • Mental Health Research Institute of Victoria, Department of Pathology, The University of Melbourne, Australia
    • Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, United States
    • Corresponding Author InformationCorresponding author at: Mental Health Research Institute of Victoria, 155 Oak Street, Parkville, Victoria 3052, Australia. Tel.: +61 39389 2952; fax: +61 39387 5061.

Received 14 June 2007 ,Revised 15 October 2007 ,Accepted 25 October 2007.

References 

  1. Andreasen N, Hesse C, Davidsson P, Wallin A, Minthon L, Winblad B, et al. Cerebrospinal fluid β-amyloid(1-42) in Alzheimer's disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease. Arch. Neurol. 1999;56:673–680
  2. Atwood CS, Moir RD, Huang X, Bacarra NME, Scarpa RC, Romano DM, et al. Dramatic aggregation of Alzheimer Aβ by Cu(II) is induced by conditions representing physiological acidosis. J. Biol. Chem. 1998;273:12817–12826
  3. Basun H, Forssell LG, Wetterberg L, Winblad B. Metals and trace elements in plasma and cerebrospinal fluid in normal aging and Alzheimer's disease. J. Neural Transm. Park. Dis. Dement. Sect. 1991;3(4):231–258
  4. Bateman RJ, Munsell LY, Morris JC, Swarm R, Yarasheski KE, Holtzman DM. Human amyloid-beta synthesis and clearance rates as measured in cerebrospinal fluid in vivo. Nat. Med. 2006;12(7):856–861
  5. Brody DL, Holtzman DM. Morris water maze search strategy analysis in PDAPP mice before and after experimental traumatic brain injury. Exp. Neurol. 2006;197(2):330–340
  6. Brown AM, Tummolo DM, Rhodes KJ, Hofmann JR, Jacobsen JS, Sonnenberg-Reines J. Selective aggregation of endogenous β-amyloid peptide and soluble amyloid precursor protein in cerebrospinal fluid by zinc. J. Neurochem. 1997;69(3):1204–1212
  7. Bush AI. The metallobiology of Alzheimer's disease. TINS. 2003;26(4):207–214
  8. Bush AI, Pettingell WH, Paradis MD, Tanzi RE. Modulation of Aβ adhesiveness and secretase site cleavage by zinc. J. Biol. Chem. 1994;269:12152–12158
  9. Bush AI, Pettingell WH, Multhaup G, Paradis MD, Vonsattel JP, Gusella JF, et al. Rapid induction of Alzheimer Aß amyloid formation by zinc. Science. 1994;265:1464–1467
  10. Bush AI, Moir RD, Rosenkranz KM, Tanzi RE. Zinc and Alzheimer's disease. Science. 1995;268:1921–1923
  11. Buxbaum JD, Liu KN, Luo Y, Slack JL, Stocking KL, Peschon JJ, et al. Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor. J. Biol. Chem. 1998;273(43):27765–27767
  12. Cherny RA, Legg JT, McLean CA, Fairlie D, Huang X, Atwood CS, et al. Aqueous dissolution of Alzheimer's disease Aß amyloid deposits by biometal depletion. J. Biol. Chem. 1999;274:23223–23228
  13. Cherny RA, Atwood CS, Xilinas ME, Gray DN, Jones WD, McLean CA, et al. Treatment with a copper-zinc chelator markedly and rapidly inhibits β-amyloid accumulation in Alzheimer's disease transgenic mice. Neuron. 2001;30:665–676
  14. Dong J, Atwood CS, Anderson VE, Siedlak SL, Smith MA, Perry G, et al. Metal binding and oxidation of amyloid-beta within isolated senile plaque cores: Raman microscopic evidence. Biochemistry. 2003;42(10):2768–2773
  15. Du Y, Ni B, Glinn M, Dodel RC, Bales KR, Zhang Z, et al. Alpha2-Macroglobulin as Aβ-amyloid peptide-binding plasma protein. J. Neurochem. 1997;69(1):299–305
  16. Flaten TP. Aluminium as a risk factor in Alzheimer's disease, with emphasis on drinking water. Brain Res. Bull. 2001;55(2):187–196
  17. Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006;5(3):228–234
  18. Huang X, Atwood CS, Moir RD, Hartshorn MA, Vonsattel J-P, Tanzi RE, et al. Zinc-induced Alzheimer's Aβ1-40 aggregation is mediated by conformational factors. J. Biol. Chem. 1997;272:26464–26470
  19. Huang X, Atwood CS, Hartshorn MA, Multhaup G, Goldstein LE, Scarpa RC, et al. The Aβ peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry. 1999;38:7609–7616
  20. Huang X, Cuajungco MP, Atwood CS, Hartshorn MA, Tyndall J, Hanson GR, et al. Cu(II) potentiation of Alzheimer Aβ neurotoxicity: correlation with cell-free hydrogen peroxide production and metal reduction. J. Biol. Chem. 1999;274:37111–37116
  21. Ibach B, Haen E, Marienhagen J, Hajak G. Clioquinol treatment in familiar early onset of Alzheimer's disease: a case report. Pharmacopsychiatry. 2005;38(4):178–179
  22. Lee J-Y, Cole TB, Palmiter RD, Suh SW, Koh J-Y. Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 2002;99(11):7705–7710
  23. Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR. Copper, iron and zinc in Alzheimer's disease senile plaques. J. Neurol. Sci. 1998;158(1):47–52
  24. Maruyama M, Higuchi M, Takaki Y, Matsuba Y, Tanji H, Nemoto M, et al. Cerebrospinal fluid neprilysin is reduced in prodromal Alzheimer's disease. Ann. Neurol. 2005;57(6):832–842
  25. Maynard CJ, Cappai R, Volitakis I, Cherny RA, White AR, Beyreuther K, et al. Overexpression of Alzheimer's disease β-amyloid opposes the age-dependent elevations of brain copper and iron levels. J. Biol. Chem. 2002;277(47):44670–44676
  26. Maynard CJ, Cappai R, Volitakis I, Cherny RA, Masters CL, Li QX, et al. Gender and genetic background effects on brain metal levels in APP transgenic and normal mice: implications for Alzheimer beta-amyloid pathology. J. Inorg. Biochem. 2006;100(5–6):952–962
  27. McCullagh P, Nelder J. Generalized Linear Models. London, UK: Chapman and Hall; 1989;
  28. McLean C, Cherny R, Fraser F, Fuller S, Smith M, Beyreuther K, et al. Soluble pool of Aβ amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann. Neurol. 1999;46(6):860–866
  29. Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, et al. The Consortium to establish a registry for Alzheimer's disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991;41:479–486
  30. Molina JA, Jimenez-Jimenez FJ, Aguilar MV, Meseguer I, Mateos-Vega CJ, Gonzalez-Munoz MJ, et al. Cerebrospinal fluid levels of transition metals in patients with Alzheimer's disease. J. Neural Transm. 1998;105(4–5):479–488
  31. Opazo C, Huang X, Cherny R, Moir R, Roher A, White A, et al. Metalloenzyme-like activity of Alzheimer's disease β-amyloid: Cu-dependent catalytic conversion of dopamine, cholesterol and biological reducing agents to neurotoxic H2O2. J. Biol. Chem. 2002;277:40302–40308
  32. Opazo C, Luza S, Villemagne VL, Volitakis I, Rowe C, Barnham KJ, et al. Radioiodinated clioquinol as a biomarker for β-amyloid: Zn2+ complexes in Alzheimer's disease. Aging Cell. 2006;5:69–79
  33. Petrovitch H, Nelson J, Snowdon D, Davis DG, Ross GW, Li CY, et al. Microscope field size and the neuropathologic criteria for Alzheimer's disease. Neurology. 1997;49(4):1175–1176
  34. Petrovitch H, White LR, Ross GW, Steinhorn SC, Li CY, Masaki KH, et al. Accuracy of clinical criteria for AD in the Honolulu-Asia Aging Study, a population-based study. Neurology. 2001;57(2):226–234
  35. Qiu WQ, Walsh DM, Ye Z, Vekrellis K, Zhang J, Podlisny MB, et al. Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation. J. Biol. Chem. 1998;273(49):32730–32738
  36. Regland B, Lehmann W, Abedini I, Blennow K, Jonsson M, Karlsson I, et al. Treatment of Alzheimer's disease with clioquinol. Dement. Geriatr. Cogn. Disord. 2001;12(6):408–414
  37. Religa D, Strozyk D, Cherny RA, Volitakis I, Haroutunian V, Winblad B, et al. Elevated cortical zinc in Alzheimer disease. Neurology. 2006;67(1):69–75
  38. Ritchie CW, Bush AI, Mackinnon A, Macfarlane S, Mastwyk M, MacGregor L, et al. Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Aβ amyloid deposition and toxicity in Alzheimer's disease: a pilot phase 2 clinical trial. Arch. Neurol. 2003;60:1685–1691
  39. Rottkamp C, Raina A, Zhu X, Gaier E, Bush A, Atwood C, et al. Redox-active iron mediates amyloid-β toxicity. Free Radic. Biol. Med. 2001;30:447–450
  40. Schlief ML, Craig AM, Gitlin JD. NMDA receptor activation mediates copper homeostasis in hippocampal neurons. J. Neurosci. 2005;25(1):239–246
  41. Strozyk D, Blennow K, White LR, Launer LJ. CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology. 2003;60(4):652–656
  42. White L, Petrovitch H, Ross GW, Masaki KH, Abbott RD, Teng EL, et al. Prevalence of dementia in older Japanese-American men in Hawaii: the Honolulu-Asia Aging Study. JAMA. 1996;276(12):955–960
  43. White AR, Du T, Laughton KM, Volitakis I, Sharples RA, Xilinas ME, et al. Degradation of the Alzheimer disease amyloid beta-peptide by metal-dependent up-regulation of metalloprotease activity. J. Biol. Chem. 2006;281(26):17670–17680

PII: S0197-4580(07)00414-9

doi: 10.1016/j.neurobiolaging.2007.10.012

Neurobiology of Aging
Volume 30, Issue 7 , Pages 1069-1077 , July 2009

Article Tools

* Image Usage & Resolution