Journal of Bioenergetics and Biomembranes

, Volume 36, Issue 4, pp 381–386 | Cite as

Mitochondrial Dysfunction and Oxidative Damage in Alzheimer's and Parkinson's Diseases and Coenzyme Q10 as a Potential Treatment

  • M. Flint Beal


There is substantial evidence that mitochondrial dysfunction and oxidative damage may play a key role in the pathogenesis of neurodegenerative disease. Evidence supporting this in both Alzheimer's and Parkinson's diseases is continuing to accumulate. This review discusses the increasing evidence for a role of both mitochondrial dysfunction and oxidative damage in contributing to β-amyloid deposition in Alzheimer's disease. I also discuss the increasing evidence that Parkinson's disease is associated with abnormalities in the electron transport gene as well as oxidative damage. Lastly, I reviewed the potential efficacy of coenzyme Q as well as a number of other antioxidants in the treatment of both Parkinson's and Alzheimer's diseases.

Mitochondria oxidative damage free radicals Alzheimer's Parkinson's coenzyme Q10 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alam, Z. I., Daniel, S. E., Lees, A. J., Marsden, D. C., Jenner, P., and Halliwell, B. (1997). J. Neurochem. 69, 1326–1329.PubMedGoogle Scholar
  2. Anandatheerthavarada, H., Biswas, G., Robin, M.-A., and Avadhani, N. G. (2003). J. Cell Biol. 161,1–14.Google Scholar
  3. Bayer, R. E. (1992). Biochem. Cell Biol. 70, 390–403.PubMedGoogle Scholar
  4. Beal, M. F., Henshaw, R., Jenkins, B. G., Rosen, R., and Schulz, J. B. (1994). Ann. Neurol. 36, 882–888.PubMedGoogle Scholar
  5. Beal, M. F., and Matthews, R. T. (1997). Mol. Asp. Med. 18, s169–s179.Google Scholar
  6. Betarbet, R., Sherer, T. B., MacKenzie, G., Garcia-Osuna, M., Panov, A. V., and Greenamyre, J. T. (2000). Nat. Neurosci. 3, 1301–1306.PubMedGoogle Scholar
  7. Bindoff, L. A., Birch-Martin, M., Cartlidge, N. E. F., Parker, W. D., and Turbull, D. M. (1989). Lancet 1, 49.Google Scholar
  8. Borchelt, D. R., Thinakaran, G., Eckman, C. B., Lee, M. K., Davenport, F., Ratovitsky, T., Prada, C. M., Kim, G., Seekins, S., Yager, D., Slunt, H. H., Wang, R., Seeger, M., Levey, A. I., Gandy, S. E., Copeland, N. G., Jenkins, N. A., Price, D. L., Younkin, S. G., and Sisodia, S. S. (1996). Neuron 17, 1005–1013PubMedGoogle Scholar
  9. Bozner, P., Grishko, V., LeDoux, S. P., Wilson, G. L., Chyan, Y.-C., and Pappolla, M. A. (1997). J. Neuropath. Exp. Neurol. 56, 1356–1362.PubMedGoogle Scholar
  10. Busciglio, J., Pelsman, A., Wong, C., Pigino, G., Yuan, M., Mori, H., and Yankner, B. A. (2002). Neuron 33, 677–688.PubMedGoogle Scholar
  11. Busciglio, J., and Yankner, B. A. (1995). Nature 378, 776–779.PubMedGoogle Scholar
  12. Casley, C. S., Canevari, L. Land, M. J., Clark, J. B., and Sharpe, M. A. (2002). J. Neurochem. 80,91–100.PubMedGoogle Scholar
  13. Castano, E. M., Prelli, F., Wisniewski, T., Golabek, A Kumar, R. A., Soto, C., and Frangione, B. (1995). Biochem. J. 306, 599–604.PubMedGoogle Scholar
  14. Chartier-Harlin, M. C., Crawford, F., Houlden, H., Warren, A., Hughes, D., Fidani, L., Goate, A., Rossor, M., Roques, P., Hardy J., et al. (1991). Nature 353, 844–846.PubMedGoogle Scholar
  15. Chishti, M. A., Yang, D. S., Janus, C., Phinney, A. L., Horne, P., Pearson, J., Strome, R., Zuker, N., Loukides, J., French, J., Turner, S., Lozza, G., Grilli, M., Kunicki, S., Morissette, C., Paquette, J., Gervais, F., Bergeron, C., Fraser, P. E., Carlson, G. A., George-Hyslop, P. S., and Westaway, D. (2001). J. Biol. Chem. 276, 21562–21570.PubMedGoogle Scholar
  16. Dallner, G., and Sindelar, P. J. (2000). Free Radic. Biol. Med. 29, 285–294.PubMedGoogle Scholar
  17. De Strooper, B., Saftig, P., Craessaerts, K., Vanderstischle, H., Guhde, G., Annaert, W., Von Figura, K., and Van Leuven, F. (1998). Nature 391, 387–390PubMedGoogle Scholar
  18. Dexter, D. T., Carter, C. J., Wells, F. R., Javoy-Agid, F., Agid, Y., Lees, A., Jenner, P., and Marsden, C. D. (1989). J. Neurochem. 52, 381–389.PubMedGoogle Scholar
  19. Dexter, D. T., Holly, A. E., Flitter, W. D., Slater, T. F., Wells, F. R., Daniel, S. E., Lees, A. J., Jenner, P., and Marsden, C. D. (1994). Mov. Disorder. 9,92–97.Google Scholar
  20. Dexter, D. T., Sian, J., Rose, S., Hindmarsch, J. G., Mann, V. M., Cooper, J. M., Wells, F. R., Daniel, S. E., Lees, A. J., Schapira, A. H. V., Jenner, P., and Marsden, C. D. (1994). Ann. Neurol. 35,38–44.PubMedGoogle Scholar
  21. Drake, J., Link, C. D., and Butterfield, D. A. (2003). Neurobiol. Aging 24, 415–420.PubMedGoogle Scholar
  22. Duff, K., Eckman, C., Zehr, C., Yu, X., Prada, C. M., Perez-tur, J., Hutton, M., Buee, L., Harigaya, Y., Yager, D., Morgan, D., Gordon, M. N., Holcomb, L., Refolo, L., Zenk, B., Hardy, J., and Younkin, S. (1996). Nature 383, 710–713.PubMedGoogle Scholar
  23. Echtay, K. S., Roussel, D., St-Pierre, J., Jekabsons, M. B., Cadenas, S., Stuart, J. A., Harper, J. A., Roebuck, S. J., Morrison, A., Pickering, S., Clapham, J. C., and Brand, M. D. (2002). Nature 415,96–99.PubMedGoogle Scholar
  24. Echtay, K. S., Winkler, E., and Klingenberg, M. (2000). Nature 408, 609–613.PubMedGoogle Scholar
  25. Favit, A., Nicoletti, F., Scapagnini, U., and Canonico, P. L. (1992). J. Cereb. Blood Flow Metab. 12, 638.PubMedGoogle Scholar
  26. Feigin, A., Kieburtz, K., Como, P., Hickey, C., Claude, K., Abwendere, D., Zimmerman, C., Steinberg, K., and Shoulson, I. (1996). Mov. Dis. 11, 321–323.Google Scholar
  27. Ferrante, R. J., Andreassen, O. A., Dedeoglu, A., Ferrante, K. L., Jenkins, B. G., Hersch, S. M., and Beal, M. F. (2002). J. Neurosci. 22, 1592–1599.PubMedGoogle Scholar
  28. Gabuzda, D., Busciglio, J., Chen, L. B., Matsudaira, P., and Yankner, B. A. (1994). J. Biol. Chem. 269, 13623–13628.PubMedGoogle Scholar
  29. Giasson, B. I., Duda, J. E., Murray, I. V. J., Chen, Q., Souza, J. M., Hurtig, H. I., Ischiropoulos, H., Trojanowski, J. Q., and Lee, V. M.-Y. (2000). Sci. Mag. 290, 985–989.Google Scholar
  30. Gibson, G. E., Zhang, H., Sheu, K. F.-R., Bogdanovich, N., Lindsay, J. G., Lannfelt, L., Vestling, M., and Cowburn, R. F. (1998). Ann. Neurol. 44, 671–681.Google Scholar
  31. Good, P. F., Hsu, A., Werner, P., Perl, D. P., and Olanow, C. W. (1998). J. Neuropathol. Exp. Neurol. 57, 338–342.PubMedGoogle Scholar
  32. Gu, M., Cooper, J. M., Taanman, J. W., and Schapira, A. H. V. (1998). Ann. Neurol. 44, 177–186.PubMedGoogle Scholar
  33. Gu, G., Reyes, P. F., Golden, G. T., Woltjer, R. L., Hulette, C., Montine, T. J., and Zharg, J. (2002). J. Neuropathol. Exp. Neurol. 61, 634–639.PubMedGoogle Scholar
  34. Hattori, N., Tanaka, M., Ozawa, T., and Mizuno, Y. (1991). Ann. Neurol. 30, 563–571.PubMedGoogle Scholar
  35. Hausse, B. O., Aggoun, Y., Bonnet, D., Sidi, D., Munnich, A., Rotig, A., and Rustin, P. (2002). Heart 87, 346.PubMedGoogle Scholar
  36. Hirai, K., Aliev, G., Nunomura, A., Fujioka, H., Russell, R. L., Atwood, C. S., Johnson, A. B., Kress, Y., Vinters, H. V., Tabaton, M., Shimohama, S., Cash, A. D., Siedlak, S. L., Harris, P. L., Jones, P. K., Petersen, R. B., Perry, G., and Smith, M. A. (2001). J. Neurosci. 21, 3017–3023.PubMedGoogle Scholar
  37. Horvath, T. L., Diano, S., Leranth, C., Garcia-Segura, L. M., Cowley, M. A., Shanabrough, M., Elsworth, J. D., Sotonyi, P., Roth, R. H., Dietrich, E. H., Matthews, R. T., Barnstable, C. J., and Edmond, D. E., Jr. (2003). Endocrinology 144, 2757–2760.PubMedGoogle Scholar
  38. Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., and Cole, G. (1996). Science 274,99–102.PubMedGoogle Scholar
  39. Janetzky, B., Hauck, S., Youdim, M. B., Riederer, P., Jellinger, K., Pantucek, F., Zochling, R., Boissl, K. W., Reichmann, H. (1994). Neurosci. Lett. 169, 126–128.PubMedGoogle Scholar
  40. Jenner, P. (2003). Ann. Neurol. 53, S26–S28.PubMedGoogle Scholar
  41. Kanamori, T., Nishimaki, K., Asoh, S., Ishibashi, Y., Takata, I., Kuwabara, T., Taira, K., Yamaguchi, H., Sugihara, S., Yamazaki, T., Ihara, Y., Nakano, K., Matuda, S., and Ohta, S. (2003). EMBO J. 22, 2913–2923.PubMedGoogle Scholar
  42. Kaneko, I., Yamada, N., Sakuraba, Y., Kamenosono, M., and Tutumi, S. (1995). J. Neurochem. 65, 2585–2593.PubMedGoogle Scholar
  43. Kang, J., Lemaire, H. G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K. H., Multhaup, G., Beyreuther, K., and Muller-Hill, B. (1987). Nature 325, 733–736PubMedGoogle Scholar
  44. Kikuchi, A., Takeda, A., Onodera, H., Kimpara, T., Hisanaga, K., Sato, N., Nunomura, A., Castellani, R. J., Perry, G., Smith, M. A., and Itoyama, Y. (2002). Neurobiol. Dis. 9, 244–248.PubMedGoogle Scholar
  45. Kingsbury, A. E., Cooper, M., Schapira, A. H. V., Foster, O. J. F. (2001). Ann. Neurol. 50, 142–149.PubMedGoogle Scholar
  46. Korozhetz, W. J., Jenkins, B. G., Rosen, B. R., and Beal, M. F. (1997). Ann. Neurol. 41, 160–165.PubMedGoogle Scholar
  47. Le Bars, P. L., Katz, M. M., Berman, N., Itil, T. M., Freedman, A. M., and Schatzberg, A. F. (1997). JAMA 278, 1327–1332.PubMedGoogle Scholar
  48. Lim, G. P., Chu, T., Yang, F., Beech, W., Frautschy, S. A., and Cole, G. M. (2001). J. Neurosci. 21, 8370–8377.PubMedGoogle Scholar
  49. Lodi, B., Hart, P. E., Rajagopalan, B., Taylor, D. J., Crilley, J. G., Bradley, J. L., Blamire, A. M., Manners, D., Styles, P., Schapira, A. H., and Cooper, J. M. (2001). Ann. Neurol. 49, 590–596.PubMedGoogle Scholar
  50. Mann, V. M., Cooper, J. M., Krige, D., Daniel, S. E., Schapira, A. H., Marsden, C. D. (1992). Brain 115, 333–342.PubMedGoogle Scholar
  51. Masliah, E., Sisk, A., Mallory, M., Mucke, L., Schenk, D., and Games, D. (1996). J. Neurosci. 16, 5759–5811.Google Scholar
  52. Matthews, R. T., Yang, S., Browne, S., Baik, M., and Beal, M. F. (1998). Proc. Natl. Acad. Sci. U.S.A. 95, 8892–8897PubMedGoogle Scholar
  53. Mattiasson, G., Shamloo, M., Gido, G., Mathi, K., Tomasevic, G., Yi, S., Warden, C. H., Castilho, R. F., Melcher, T., Gonzalez-Zulueta, M., Nikolich, K., and Wieloch, T. (2003). Nat. Med. 9, 1062–1068.PubMedGoogle Scholar
  54. Matsubara, E., Bryant-Thomas, T., Pacheco Quinto, J., Henry, T. L., Poeggeler, B., Herbert, D., Cruz-Sanchez, F., Chyan, Y. J., Smith, M. A., Perry, G., Shoji, M., Abe, K., Leone, A., Grundke-Ikbal, I., Wilson, G. L., Ghiso, J., Williams, C., Refolo, L. M., and Pappolla, M. A. (2003). J. Neurochem. 85, 1101–1108.PubMedGoogle Scholar
  55. Migliore, L., Petrozzi, L., Lucetti, C., Gambaccini, G., Bernadini, S., Scarpato, R., Trippi, F., Barale, R., Frenzilli, G., Rodilla, V., and Bonuccelli, U. (2002). Neurology 58, 1809–1815.PubMedGoogle Scholar
  56. Mullan, M., Crawford, F., Axelman, K., Houlden, H., Lilius, L., Winbald, B., and Lannfelt, L. (1992). Nat. Genet. 1, 345–347.PubMedGoogle Scholar
  57. Noack, H., Kube, U., and Augustin, W. (1994). Free Radic. Res. 20, 375–386.PubMedGoogle Scholar
  58. Nunomura, A., Perry, G., Aliev, G., Hirai, K., Takeda, A., Balraj, E. K., Jones, P. K., Ghanbari, H., Wataya, T., Shimohama, S., Chiba, S., Atwood, C. S., Petersen, R. B., and Smith, M. A. (2001). J. Neuropathol. Exp. Neurol. 60, 759–767.PubMedGoogle Scholar
  59. Nunomura, A., Perry, G., Pappolla, M. A., Friedland, R. P., Hirai, K., Chiba, S., and Smith, M. A. (2000). J. Neuropathol. Exp. Neurol. 59, 1011–1017.PubMedGoogle Scholar
  60. Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., and LaFerla, F. M. (2003). Neuron 39, 409–421.PubMedGoogle Scholar
  61. Ohyagi, Y., Yamada, T., Nishioka, K., Clarke, N. J., Tomlinson, A. J., Naylor, S., Nakabeppu, Y., Kira, J., and Younkin, S. G. (2000). Neuroreport 11, 167–171.PubMedGoogle Scholar
  62. Oken, B. S., Storzbach, D. M., and Kaye, J. A. (1998). Arch. Neurol. 55, 1409–1415.PubMedGoogle Scholar
  63. Olson, M. I., and Shaw, C. M. (1969). Brain 92, 147–156.PubMedGoogle Scholar
  64. Ostrowski, R. P. (2000). Brain Res. Bull. 53, 399–407.PubMedGoogle Scholar
  65. Pappolla, M. A., Chyan, Y.-J., Omar, R. A., Hsiao, K., Perry, G., Smith, M. A., and Bozner, P. (1998). Am. J. Pathol. 152, 871–877.PubMedGoogle Scholar
  66. Papucci, L., Schiavone, N., Witort, E., Donnini, M., Lapucci, A., Tempestini, A., Formigli, L., Zecchi-Orlandini, S., Orlandini, G., Carella, G., Brancato, R., and Capaccioli, S. (2003). J. Biol. Chem. 278, 28220–28228.PubMedGoogle Scholar
  67. Paxinou, E., Chen, Q., Weisse, M., Giasson, B. I., Norris, E. H., Rueter, S. M., Trojanowski, J. G., Lee, V. M.-Y., and Ischiropoulos, H. (2001). J. Neurosci. 21, 8053–8061.PubMedGoogle Scholar
  68. Perry, T. L., Godin, D. V., and Hansen, S. (1982). Neurosci. Lett. 33, 305–310.PubMedGoogle Scholar
  69. Perry, T. L., and Yong, V. W. (1986). Neurosci. Lett. 67, 269–274.PubMedGoogle Scholar
  70. Pratico, D., Uryu, K., Leight, S., Trojanoswki, J. Q., and Lee, V. M. (2001). J. Neurosci. 21, 4183–4187PubMedGoogle Scholar
  71. Rana, M., de Coo, I., Diaz, F., Smeets, H., and Moraes, C. T. (2000). Ann. Neurol. 48, 774–781.PubMedGoogle Scholar
  72. Richter, G., Sonneschein, A., Grunewald, T., Reichmann, H., and Janetzky, B. (2002). J. Neural. Transm. 109, 721–729.PubMedGoogle Scholar
  73. Riederer, P., Park, J.-W., and Ames, B. (1989). J. Neruochem. 52, 515–520.Google Scholar
  74. Rustin, P., von Kleist-Retzow, J. C., Chantrel-Groussard, K., Sidi, D., Munnich, A., and Rotig, A. (1999). Lancet 354, 477–479.PubMedGoogle Scholar
  75. Sanchez-Ramos, J. R., Overvik, E., and Ames, B. N. (1994). Neurode-generation 3, 197–204.Google Scholar
  76. Sano, M., Ernesto, C., Thomas, R. G., Klauber, M. R., Schafer, K., Grundman, M., Woodbury, P., Growdon, J., Cotman, C. W., Pfeiffer, E., Schneider, L. S., and Thal, L. J. (1997). The Alzheimer's Disease Cooperative Study, N. Engl. J. Med. 336, 1216–1222.Google Scholar
  77. Schapira, A. H. V., Cooper, J. M., Dexter, D., Clark, J. B., Jenner, P., and Marsden, C. D. (1990). J. Neurochem. 54, 823–827.PubMedGoogle Scholar
  78. Scherer, T. B., Betarbet, R., Stout, A. K., Lund, S., Baptista, M., Panov, A. V., Cookson, M. R., Greenamyre, J. T. (2002). J. Neurosci. 22, 7006–7015.PubMedGoogle Scholar
  79. Shearman, M. S., Ragan, C. I., and Iversen, L. L. (1994). Proc. Natl. Acad. Sci. U.S.A. 91, 1470–1474.PubMedGoogle Scholar
  80. Sheehan, J. P., Swerdlow, R. H., Parker, W. D., Miller, S. W., Davis, R. E., and Tuttle, J. B. (1997). J. Neurochem. 68, 1221–1233.PubMedGoogle Scholar
  81. Shergill, J. K., Cammack, R., Cooper, C. E., Cooper, J. M., Mann, V. M., and Schapira, A. H. V. (1996). Biochem. Biophys. Res. Commun. 228, 298–305.PubMedGoogle Scholar
  82. Sheu, R.-K., F., Cooper, A. J., Koike, K., Koike, M., Lindsay, J. G., and Blass, J. P. (1994). Ann. Neurol. 35, 312–318.PubMedGoogle Scholar
  83. Shults, C. W., Oakes, D., Kieburtz, K., Beal, M. F., Haas, R., Plumb, S., Juncos, J. L., Nutt, J., Shoulson, I., Carter, J., Kompoliti, K., Perlmutter, J. S., Reich, S., Stern, M., Watts, R. L., Kurlan, R., Molho, E., Harrison, M., and Lew, M. (2002). Parkinson Study Group. Arch. Neurol. 59, 1541–1550.Google Scholar
  84. Simon, D. K., Mayeux, R., Marder, K., Kowall, N. W., Beal, M. F., and Johns, D. R. (2000). Neurology 54, 703–709.PubMedGoogle Scholar
  85. Simon, D. K., Pulst, S. M., Sutton, J. P., Browne, S. E., Beal, M. F., and Johns, D. R. (1999). Neurology 53, 1787–1793.PubMedGoogle Scholar
  86. Smith, M. A., Hirai, K., Hsiao, K., Pappolla, M. A., Harris, P. L. R., Siedlak, S. L., Tabaton, M., and Perry, G. (1998). J. Neurochem. 70, 2212–2215.PubMedGoogle Scholar
  87. Soficm, E., Lange, K. W., Jellinger, K., and Reiderer, P. (1992). Neurosci. Lett. 142, 128–130.PubMedGoogle Scholar
  88. Strittmatter, W. J., Weisgraber, K. H., Huang, D. Y., Dong, L. M., Salvesen, G. S., Pericak-Vance, M., Schmechel, D., Saunders, A. M., Goldgaber, D., and Roses, A. D. (1993). Proc. Natl. Acad. Sci. U.S.A. 90, 8098–8102.PubMedGoogle Scholar
  89. Sturchler-Pierrat, C., Abramowski, D., Duke, M. W., Mistl, K.-H. C., Rothacher, S., Ledermann, B., Burki, K., Frey, P., Pagnetti, P. A., Waridel, C., Calhoun, M. E., Jucker, M., Probst, A., Staufenbiel, M., and Sommer, B. (1997). Proc. Natl. Acad. Sci. U.S.A. 94, 13287–13292PubMedGoogle Scholar
  90. Sullivan, P. G., Dube, C., Dorenbos, K., Steward, O., and Baram, T. Z. (2003). Ann. Neurol. 53, 711–717.PubMedGoogle Scholar
  91. Swerdlow, R. H., Parks, J. K., Miller, S. W., Tuttle, J. B., Trimmer, P. A., Shehan, J. P., Bennett, J. P., Jr., Davis, R. E., and Parker, W. D., Jr. (1996). Ann. Neurol. 40, 663–671.PubMedGoogle Scholar
  92. Tamagno, E., Bardini, P., Obbili, A., Vitali, A., Borghi, R., Zaccheo, D., Pronzato, M. A., Danni, O., Smith, M. A., Perry, G., and Tabaton, M. (2002). Neurobio. Dis. 10, 279–288.Google Scholar
  93. The Huntington Study Group. (2001). Neurology 57, 397–404Google Scholar
  94. Thyagarajan, D., Bressman, S., Bruno, C., Przedborski, S., Shanske, S., Lynch, T., Fahn, S., and DiMauro, S. (2000). Ann. Neurol. 48, 730–736.PubMedGoogle Scholar
  95. Van der Walt, J. M., Nicodemus, K. K., Martin, E. R., Scott, W. K., Nance, M. A., Watts, R. L., Hubble, J. P., Haines, J. L., Koller, W. C., Lyons, K., Pahwa, R., Stern, M. B., Colcher, A., Hiner, B. C., Jankovic, J., Ondo, W. G., Allen, F. H., Goetz, C. G., Small, G. W., Mastaglia, F., Stajich, J. M., McLaurin, A. C., Middleton, L. T., Scott, B. L., Schmechel, D. E., Pericak-Vance, M. A., and Vance, J. M. (2003). Am. J. Hum. Genet. 72, 804–811.PubMedGoogle Scholar
  96. Williams, M. D., Van Remmen, H., Conrad, C. C., Huang, T. T., Epstein, C. J., and Richardson, A. (1998). J. Biol. Chem. 273, 28510–28515.PubMedGoogle Scholar
  97. Wisniewski, T., Dowjat, W. K., Permanne, B., Palha, J., Kumar, A., Gallo, G., and Frangione, B. (1997). Am. J. Pathol. 15, 601–610.Google Scholar
  98. Wolfe, M. S., Xia, W., Ostaszewski, B. L., Diehl, T. S., Kimberly, W. T., and Selkoe, D. J. (1999). Nature 398, 513–517.PubMedGoogle Scholar
  99. Zhang, J., Perry, G., Smith, M. A., Robertson, D., Olson, S. J., Graham, D. G., and Montine, T. J. (1999). Am. J. Pathol. 154, 1423–1429.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2004

Authors and Affiliations

  • M. Flint Beal
    • 1
  1. 1.Department of Neurology and NeuroscienceNew York Presbyterian Hospital-Weill Medical College of Cornell UniversityNew YorkNew York 10021

Personalised recommendations