Alzheimer's disease, β-amyloid protein and zinc

Journal of Nutrition

Volumn 130, Issue 5 SUPPL., 2000, Pages

  Huang, Xudong ^a   Cuajungco, Math P ^a   Atwood, Craig S ^a   Moir, Robert D ^a   Tanzi, Rudolph E ^a   Bush, Ashley I ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Alzheimer's disease; Amyloid precursor protein; A amyloid; Homeostasis; Zinc

Indexed keywords

ALPHA 2 MACROGLOBULIN; AMYLOID BETA PROTEIN; APOLIPOPROTEIN E; COPPER; HYDROGEN PEROXIDE; IRON; METALLOPROTEIN; ZINC;

ALZHEIMER DISEASE; CONFERENCE PAPER; HOMEOSTASIS; HUMAN; NEUROTOXICITY; OXIDATIVE STRESS; PROTEIN PROCESSING; PROTEIN STRUCTURE; RISK FACTOR; SUPPLEMENTATION;

EID: 0034054929     PISSN: 00223166     EISSN: None     Source Type: Journal    
DOI: 10.1093/jn/130.5.1488s     Document Type: Conference Paper

References (94)

1. Ancsin, J. B. & Kisilevsky, R. (1996) Laminin interactions important for basement membrane assembly are promoted by zinc and implicate laminin zinc finger-like sequences. J. Biol. Chem. 271: 6845-6851.
2. 2+ from brain tissue during activity. Nature (Lond.) 308: 734-736.
3. Beaulieu, C., Dyck, R. & Cynader, M. (1992) Enrichment of glutamate in zinc-containing terminals of the cat visual cortex. Neuroreport 3: 861-864.
4. Behl, C., Davis, D. R., Lesley, R. & Schubert, D. (1994) Hydrogen peroxide mediates amyloid β protein toxicity. Cell 77: 817-827.
5. Berg, J. L. & Shi, Y. (1996) The galvanization of biology: a growing appreciation for the roles of zinc. Science (Washington, DC) 271: 1081-1085.
6. Blacker, D., Wilcox, M. A., Laird, N. M., Rodes, L., Horvath, S. M., Go, R.C.P., Perry, R., Watson, B., Jr., Basset, S. S., McInnis, M. G., Albert, M. S., Hyman, B. T. & Tanzi, R. E. (1998) Alpha-2 macroglobulin is genetically associated with Alzheimer's disease. Nat. Genet. 19: 357-360.
7. Blair-West, J. R., Denton, D. A., Gibson, A. P. & McKinely, M. J. (1990) Opening the blood-brain barrier to zinc. Brain Res. 507: 6-10.
8. Bronfman, F. C., Garrido, J., Alvarez, A., Morgan, C. & Inestrosa, N. C. (1996) Laminin inhibits amyloid-β-peptide fibrillation. Neurosci. Lett. 218: 201-203.
9. Bruce, A. J., Malfroy, B. & Baudry, M. (1996) β-Amyloid toxicity in organotypic hippocampal cultures: protection by EUK-8, a synthetic catalytic free radical scavenger. Proc. Natl. Acad. Sci. U.S.A. 93: 2312-2316.
10. Bush, A. I., Multhaup, G., Moir, R. D., Williamson, T. G., Small, D. H., Rumble, B., Pollwein, P., Beyreuther, K. & Masters, C. L. (1993) A novel zinc(II) binding site modulates the function of the A4β amyloid protein precursor of Alzheimer's disease. J. Biol. Chem. 268: 16109-16112.
11. Bush, A. L., Pettingel, W. H., Multhaup, G., Paradis, M. D., Vonsattel, J. P., Gusella, J. F., Beyreuther, K., Masters, C. L. & Tanzi, R. E. (1994a) Rapid induction of Alzheimer Aβ amyloid formation by zinc. Science (Washington, DC) 265: 1467.
12. Bush, A. I., Pettingel, W. H., Paradis, M. D. & Tanzi, R. E. (1994c) Modulation of Aβ adhesiveness and α-secretase site cleavage by zinc. J. Biol. Chem. 269: 12158.
13. Bush, A. I., Pettingel, W. H., Paradis, M. D., Tanzi, R. E. & Wasco, W. (1994b) The amyloid β-protein precursor and its mammalian homologues. J. Biol. Chem. 269: 26618-26621.
14. Butterfield, D. A., Hensley, K., Harris, M., Mattson, M. P. & Carney, J. M. (1994) β-Amyloid peptide free radical fragments initiate synaptosomal lipoperoxidation in a sequence-specific fashion: implications to Alzheimer's disease. Biochem. Biophys. Res. Commun. 200: 710-715.
15. Chartier-Harlin, M. C., Crawford, F. & Houlden, H. (1991) Early-onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein gene. Nature (Lond.) 353: 844-846.
16. Cherny, R. A., Masters, C. L., Beyreuther, K., Fairlie, D., Tanzi, R. E. & Bush, A. I. (1997) The aggregation of Aβ in human brain is mediated by zinc. Soc. Netrosci. Abstr. 23: 534.
17. Choi, D. W. & Koh, J. Y. (1998) Zinc and brain injury. Annu. Rev. Neurosci. 21: 347-375.
18. Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G., Johnson-Wood, K., Lee, M., Seubert, P., David, A., Kholodenko, D., Motter, R., Sherrington, R., Perry, B., Yao, H., Strome, R., Lieberburg, I., Rommens, J., Kim, S., Schenk, D., Fraser, P., St. George-Hyslop, P. H. & Selkoe, D. J. (1997) Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. Nat. Med. 3: 67-72.
19. Constantinidis, J. (1990) Alzheimer's disease: the zinc theory. L'Encephale 16: 231-239.
20. Cornett, C. R., Markesbery, W. R. & Ehmann, W. D. (1998) Imbalances of trace elements related to oxidative damage in Alzheimer's disease brain. Neurotoxicology 19: 339-345.
21. Corrigan, F. M., Reynolds, G. P. & Ward, N. I. (1993) Hippocampal tin, aluminum, and zinc in Alzheimer's disease. Biometals 6: 154.
22. Cuajungco, M. P. & Lees, G. J. (1997a) Zinc and Alzheimer's disease: is there a direct link? Brain Res. Rev. 23: 219-236.
23. Cuajungco, M. P. & Lees, G. J. (1997b) Zinc metabolism in the brain: relevance to human neurodegenerative disorders. Neurobiol. Dis. 4: 137-169.
24. Cummings, J. L., Vinters, H. V., Cole, G. M. & Khachaturian, Z. S. (1998) Alzheimer's disease: etiologies, pathophysiology, cognitive reserve, and treatment opportunities. Neurology 51: S2-S17.
25. Danscher, G., Jensen, K. B., Frederickson, C. J., Kemp, K., Andreasen, A., Juhl, S., Stoltenberg, M. & Ravid, R. (1997) Increased amount of zinc in the hippocampus and amygdala of Alzheimer's diseased brains: a proton-induced x-ray emission spectroscopic analysis of cryostat sections from autopsy material. J. Neurosci. Methods 76: 53-59.
26. Deibel, M. A., Ehmann, W. D. & Markesbery, W. R. (1996) Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer's disease: possible relation to oxidative stress. J. Neural. Sci. 143: 137-142.
27. Deng, Q. S., Turk, G. C., Brady, D. R. & Smith, Q. R. (1994) Evaluation of brain element composition in Alzheimer's disease using inductively-coupled plasma mass spectrometry. Neurobiol. Aging 15: S113.
28. 2-Macroglobulin attenuates β-amyloid peptide 1-40 fibril formation and associated neurotoxicity in cultured fetal rat cortical neurons. J. Neurochem. 70: 1182-1188.
29. 2-Macroglobulin as a β-amyloid peptide-binding plasma protein. J. Neurochem. 69: 299-305.
30. Esch, F. S., Keim, P. S., Beatte, E. C., Blacher, R. W., Culwell, A. R., Oltersdorf, T., McClure, D. & Ward, P. J. (1990) Cleavage of amyloid β peptide during constitutive processing of its precursor. Science (Washington, DC) 248: 1122-1124.
31. Esler, W. P., Stimson, E. R., Jennings, J. M., Ghilardi, J. R., Mantyh, P. W. & Maggio, J. E. (1996) Zinc-induced aggregation of human and rat β-amyloid peptides in vitro J. Neurochem. 66: 723-732.
32. Fliss, H. & Menard, M. (1992) Oxidant-induced mobilization of zinc from metallothionein. Arch. Biochem. Biophys. 293: 195-199.
33. Frederickson, C. J., Howell, G. & Kasarskis, E. J. (1984) The Neurobiology of Zinc. Part B: Deficiency, Toxicity and Pathology. Alan R. Liss, New York.
34. Garzon-Rodriguez, W., Sepulveda-Becerra, M., Milton, S. & Glabe, C.G. (1997) Soluble amyloid Aβ(1-40) exists as a stable dimer at low concentrations. J. Biol. Chem. 272: 21037-21044.
35. Glenner, G. G. & Wong, C. (1984) Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 120: 885-890.
36. Haass, C., Schlossmacher, M. G., Hung, A. Y., Vigo-Pelfrey, C., Mellon, A., Ostaszewski, B. L., Leiberburg, I., Koo, E. H., Schenk, D., Teplow, D. B. & Selkoe, D. J. (1992) Amyloid β-peptide is produced by cultured cells during normal metabolism. Nature (Lond.) 359: 322-325.
37. Hensley, K., Camey, J. M., Mattson, M. P., Aksenova, M. V., Harris, M., Wu, J. F., Floyd, R. A. & Butterfield, D. A. (1994) A model for β-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Prac. Natl. Acad. Sci. U.S.A. 91: 3270-3274.
38. Hensley, K., Hall, N., Subramaniam, R., Cole, P., Harris, M., Aksenov, M., Aksenova, M. V., Gabbita, S. P., Wu, J. F., Carney, J. M., Lovell, M. A., Markesbery, W. R. & Butterfield, D. A. (1995) Brain regional correspondence between Alzheimer's disease histopathology and biomarkers of protein oxidation. J. Neurochem. 65: 2146-2156.
39. Hilbich, C., Kisters-Woike, B., Reed, J., Masters, C. L. & Beyreuther, K. (1991) Aggregation and secondary structure of synthetic amyloid βA4 peptides of Alzheimer's disease. J. Mol. Biol. 218: 149-163.
40. Howell, G. A., Welch, M. G. & Frederickson, C. J. (1984) Stimulation-induced uptake and release of zinc in hippocampal slices. Nature (Lond.) 308: 736-738.
41. Hsiao, K., Borchelt, D. R., Olson, K., Johannsdottir, R., Kitt, C., Yunis, W., Xu, S., Eckman, C., Younkin, S., Price, D. L., Iadecola, C., Clark, H. B. & Cartson, G. (1995) Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins. Neuron 15: 1203-1218.
42. Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F. & Cole, G. (1996) Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science (Washington, DC) 274: 99-102.
43. Huang, X., Atwood, C. S., Goldstein, L. E., Hartshorn, M. A., Moir, R. D., Multhaup, G., Tanzi, R. E. & Bush, A. I. (1997b) Alzheimer Aβ peptides simultaneously reduce metals and produce reactive oxygen species. Sec. Neurosci. Abstr. 23: 1663.
44. Huang, X., Atwood, C. S., Moir, R. D., Hartshorn, M. A., Vonsattel, J. P., Tanzi, R. E. & Bush, A. I. (1997a) Zinc-induced Alzheimer's Aβ1-40 aggregation is mediated by conformational factors. J. Biol. Chem. 272: 26464-26470.
45. 2-Macroglobulin associates with β-amyloid peptide and prevents fibril formation. Proc. Natl. Acad. Sci. U.S.A. 95: 3275-3280.
46. Jarrett, J. T., Berger, E. P. & Lansbury, P. T. (1993) The carboxy terminus of the β amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease. Biochemistry 32: 4693-4697.
47. Kang, J., Lemaire, H., Unterbeck, A., Salbaum, M., Masters, C. L., Grzeschik, K., Multhaup, G., Beyreuther, K. & Muller-Hill, B. (1987) The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature (Lond.) 325: 733-736.
48. Kasarskis, E. J. (1984) Zinc metabolism in normal and zinc-deficient rat brain. Exp. Neurol. 85: 114-127.
49. Komiyama, Y., Murakami, T., Egawa, H., Okubo, S., Yasunaga, K. & Murata, K. (1992) Purification of factor XIa inhibitor from human platelets. Thromb. Res. 66: 397-408.
50. Levy-Lahad, E., Yu, C. E., Wasco, W., Poorkaj, P., Romano, D. M., Oshima, J., Pettingel, W. H., Jondra, P. D., Schmidt, S. D., Wang, K., Crowley, A. C., Fu, Y. H., Guenette, S. Y., Galas, D., Nemens, E., Wijsman, E. M., Bird, T. D., Schellenberg, G. D. & Tanzi, R. E. (1995) Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science (Washington, DC) 269: 973-977.
51. Lorenzo, A. & Yankner, B. A. (1994) β-Amyloid neurotoxicity requires fibril formation and is inhibited by Congo red. Proc. Natl. Acad. Sci. U.S.A. 91: 12243-12247.
52. Lovell, M. A., Robertson, J. D., Teesdale, W. J., Campbell, J. L. & Markesbery, W. R. (1998) Copper, iron and zinc in Alzheimer's disease senile plaques. J. Neurol. Sci. 158: 47-52.
53. Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L. & Beyreuther, K. (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc. Natl. Acad. Sci. U.S.A. 82: 4245-4249.
54. McGeer, P. L. & McGeer, E. G. (1995) The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res. Rev. 21: 195-218.
55. Monji, A., Tashiro, K., Yoshida, I., Hayashi, Y. & Tashiro, N. (1998) Laminin inhibits A beta 40 fibril formation promoted by apolipoprotein E4 in vitro. Brain Res. 796: 171-175.
56. Motter, R., Vigo-Pelfrey, C., Kholodenko, D., Barbour, R., Johnson-Wood, K., Galasko, D., Chang, L., Miller, B., Clark, C., Green, R., Olson, D., Southwick, P., Wolfert, R., Munroe, B., Leiberburg, I., Seubert, P., & Schenk, D. (1995) Reduction of β-amyloid peptide 42 in the cerebrospinal fluid of patients with Alzheimer's disease. Ann. Neurol. 38: 643-648.
57. Multhaup, G., Bush, A. I., Pollwein, P. & Masters, C. L. (1994) Interaction between the zinc(II) and the heparin binding site of the Alzheimer's disease A4β amyloid precursor protein. FEBS Lett. 355: 151-154.
58. Murrell, J., Ghetti, B. & Benson, M. (1991) A mutation in the amyloid precursor protein associated with Alzheimer's disease. Science (Washington, DC) 254: 97-99.
59. Nakamura, T., Shoji, M., Harigaya, Y., Watanabe, M., Hosoda, K., Cheung, T. T., Shaffer, L. M., Golde, T. E., Younkin, L. H., Younkin, S. G. & Hirai, S. (1994) Amyloid β protein levels in cerebrospinal fluid are elevated in early-onset Alzheimer's disease. Ann. Neurol. 36: 903-911.
60. Narindrasorasak, S., Lowery, D. E., Altman, R. A., Gonzales-DeWhitt, P., Greenberg, B. D. & Kisilevsky, R. (1992) Characterization of high affinity binding between laminin and Alzheimer's disease amyloid precursor proteins. Lab. Invest. 67: 643-652.
61. 2-Macroglobulin complexes with and mediates the endocytosis of α-amyloid peptide via cell surface low-density lipoprotein receptor-related protein. J. Neurochem. 69: 1904-1911.
62. Penkowa, M. & Moos, T. (1995) Disruption of the blood-brain interface in neonatal rat neocortex induces a transient expression of metallothionein in reactive astrocytes. Glia 13: 217-227.
63. Perry, D. K., Smyth, M. J., Stennicke, H. R., Salvesen, G. S., Duriez, P., Poirier, G. G. & Hannun, Y. A. (1997) Zinc is a potent inhibitor of the apoptotic protease, caspase-3: a novel target for zinc in the inhibition of apoptosis. J. Biol. Chem. 272: 18530-18533.
64. Pike, C. J., Walencewicz, A. J., Glabe, C. G. & Cotman, C. W. (1991) Aggregation-related toxicity of synthetic α-amyloid protein in hippocampal cultures. Eur. J. Pharmacol. 207: 367-368.
65. Potocnik, F. C., van Rensburg, S. J., Park, C., Taljaard, J.J.F. & Emsley, R. A. (1997) Zinc and platelet membrane microviscosity in Alzheimer's disease: the in vivo effect of zinc on platelet membranes and cognition. South Afr. Med. J. 87: 1116-1119.
66. Prasad, A. S. (1998) Zinc in human health: an update. J. Trace Elem. Exp. Med. 11:63-87.
67. Prelli, F., Castano, E., Glenner, G. G. & Frangione, B. (1988) Differences between vascular and plaque core amyloid in Alzheimer's disease. J. Neurochem. 51: 648-651.
68. 2-macroglobulin complex. J. Biol. Chem. 271: 8443-8451.
69. 2-macroglobulin receptor/low-density lipoprotein receptor-related protein. Ann. Neurol. 37: 211-217.
70. Robakis, N. K., Ramakrishna, N., Wolfe, G. & Wisniewski, H. M. (1987) Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides. [published erratum appears in Proc. Natl. Acad. Sci. U.S.A. 84: 7721] Proc. Natl. Acad. Sci. U.S.A. 84: 4190-4194.
71. Roberts, S. B., Ripellino, J. A., Ingalls, K. M., Robakis, N. K. & Felsentein, K. M. (1994) Non-amyloidogenic cleavage of the β-amyloid precursor protein by an integral membrane metalloendopeptidase. J. Biol. Chem. 269: 3111-3116.
72. Samudralwar, D. L., Diprete, C. C., Ni, B. F., Ehmann, W. D. & Markesbery, W. R. (1995) Elemental imbalances in the olfactory pathway in Alzheimer's disease. J. Neurol. Sci. 130: 139-145.
73. Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., Hulette, C., Crain, B., Goldgaber, D. & Roses, A. D. (1993) Association of apolipoprotein E allele ∈4 with late-onset familial and sporadic Alzheimer's disease. Neurology 43: 1467-1472.
74. Seubert, P., Vigo-Pelfrey, C., Esch, F. S., Lee, M., Dovey, H., Davis, D., Sinha, S., Schlossmacher, M. G., Whaley, J., Swindlehurst, C., McCormack, R., Wolfert, R., Selkoe, D. J., Lieberberg, I. & Schenk, D. (1992) Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids. Nature (bond.) 359: 325-327.
75. Sherrington, R., Rogaev, E. I., Liang, Y., Rogaev, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., Tsuda, T., Mar, L., Foncin, J. F., Bruni, A. C., Montesi, M. P., Sorbi, S., Rainero, I., Pinessi, L., Polinsky, R. J., Wasco, W., Da Silva, H.A.R., Haines, J. L., Pericak-Vance, M. A., Tanzi, R. E., Roses, A. D., Fraser, P. E., Rommens, J. M. & St. George-Hyslop, P. H. (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature (Lond.) 375: 755-760.
76. Shivers, B. D., Hilbich, C., Multhaup, G., Salbaum, M., Beyreuther, K. & Seeburg, P. H. (1988) Alzheimer's disease amyloidogenic glycoprotein: expression pattern in rat brain suggests role in cell contact. EMBO J. 7: 1365-1370.
77. Shoji, M., Golde, T. E., Ghiso, J., Cheung, T. T., Estus, S., Shaffer, L. M., Cai, X. D., McKay, D. M., Tintner, R., Frangione, B. & Younkin, S. G. (1992) Production of the Alzheimer amyloid β protein by normal proteolytic processing. Science (Washington, DC) 258: 126-129.
78. Smith, M. A., Hsiao, K., Pappolla, M. A., Harris, P.L.R., Siedlak, S. L., Tabaton, M. & Perry, G. (1998) Amyloid-β deposition in Alzheimer transgenic mice is associated with oxidative stress. J. Neurochem. 70: 2212-2215.
79. Su, J. H., Anderson, A. J., Cummings, B. J. & Cotman, C. W. (1994) Immunohistochemical evidence for apoptosis in Alzheimer's disease. Neuroreport 5: 2529-2533.
80. Suh, S. W., Jensen, K. B., Jensen, M. S., Silva, D. S., Kesslak, J. P., Danscher, G. & Frederickson, C. J. (1998) Histologic evidence of a zinc role in Alzheimer's disease. Soc. Neurosci. Abstr. 24: 1217.
81. Suzuki, N., Cheung, T. T., Cai, X. D., Odaka, A., Otvos, L., Eckman, C., Golde, T. E. & Younkin, S. G. (1994) An increased percentage of long amyloid β protein secreted by familial amyloid β protein precursor (bAPP717) mutants. Science (Washington, DC) 264: 1336-1340.
82. Tanzi, R. E., Gusella, J. F., Watkins, P. C., Bruns, G.A.P., St. George-Hyslop, P. H., Van Keuren, M. L., Patterson, D., Pagan, S., Kurnit, D. M. & Neve, R. L. (1987) Amyloid β protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science (Washington, DC) 235: 880-884.
83. Tanzi, R. E., McClathy, A. I., Lamperti, E. D., Villa-Komaroff, L., Gusella, J. F. & Neve, R. L. (1988) Protease inhibitor domain encoded by an amyloid precursor mRNA associated with Alzheimer's disease. Nature (Lond.) 331: 528-530.
84. Teller, J. K., Russo, C., DeBusk, L. M., Angelini, G., Zaccheo, D., Dagna-Bricarelli, F., Scartezzini, P., Bertolini, S., Mann, D. M., Tabaton, M. & Gambetti, P. (1996) Presence of soluble amyloid beta-peptide precedes amyloid plaque formation in Down's syndrome, [see comments in: Nat. Med. 2: 31-32] Nat. Med. 2: 93-95.
85. Thomas, T., Thomas, G., McLendon, C., Sutton, T. & Mullan, M. (1996) β-amyloid-mediated vasoactivity and vascular endothelial damage. Nature (Lond.) 380: 168-171.
86. Thompson, C. M., Markesbery, W. R., Ehmann, W. D., Mao, Y.-X. & Vance, D. E. (1988) Regional brain trace element studies in Alzheimer's disease. Neurotoxicology 9: 1-7.
87. Van Rhijn, A. G., Prior, C. A. & Corrigan, F. M. (1990) Dietary supplementation with zinc sulphate, sodium selenite and fatly acids in early dementia of Alzheimer's type. J. Nutr. Med. 1: 259-266.
88. Vigo-Pelfrey, C., Lee, D., Keim, P., Leiberburg, I. & Schenk, D. B. (1993) Characterization of β-amyloid peptide from human cerebrospinal fluid. J. Neurochem. 61: 1965-1968.
89. Wallace, M. N., Geddes, J. G., Farquhar, D. A. & Masson, M. R. (1997) Nitric oxide synthase in reactive astrocytes adjacent to β-amyloid plaques. Exp. Neurol. 144: 266-272.
90. Wasco, W., Bupp, K., Magendantz, M., Gusella, J. F., Tanzi, R. E. & Solomon, F. (1992) Identification of a mouse brain cDNA that encodes a protein related to the Alzheimer's disease-associated β precursor protein. Proc. Natl Acad. Sci. U.S.A. 89: 10758-10762.
91. Wasco, W., Gurubhagavatula, S., Paradis, M. D., Romano, D. M., Sisodia, S. S., Hyman, B. T., Neve, R. L. & Tanzi, R. E. (1993) Isolation and characterization of the human APLP2 gene encoding a homologue of the Alzheimer's associated amyloid β protein precursor. Nat. Genet. 5: 95-100.
92. Xia, W., Zhang, J., Kholodenko, D., Citron, M., Podlisny, M. B., Teplow, D. B., Haass, C., Seubert, P., Koo, E. H. & Selkoe, D. J. (1997) Enhanced production and oligomerization of the 42-residue amyloid beta-protein by Chinese hamster ovary cells stably expressing mutant presenilins. J. Biol. Chem. 272: 7977-7982.
93. Zalewski, P. D., Forbes, I. J., Seamark, R. F., Borlinghaus, R., Belts, W. H., Lincoln, S. F. & Ward, A. (1994) Flux of intracellular labile zinc during apoptosis (gene-directed cell death) revealed by a specific chemical probe, Zinquin. Chem. Biol. 1: 153-161.
94. Zambenedetti, P., Giordano, R. & Zatta, P. (1998) Metallothioneins are highly expressed in astrocytes and microcapillaries in Alzheimer's disease. J. Chem. Neuroanat. 15: 21-26.