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Neurodegeneration in Alzheimer disease

Is apoptosis involved?

  • Part VII Apoptosis and Neurodegenerative Disorders
  • Published:
Molecular and chemical neuropathology

Abstract

Alzheimer disease (AD), the most common dementia of the elderly, results from a significant loss of neuronal cells in brain regions important in memory and cognition. Several lines of evidence suggest that the Aβ peptide is directly responsible for some of this neuronal cell death. We review recent evidence from in vitro toxicity and immunohistochemical studies that suggest some of the cell loss in AD is the result of apoptosis.

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References

  • Barr P. J. and Tomei L. D. (1994) Apoptosis and its role in human disease.BioTechnology (NY) 12, 487–493.

    Article  CAS  Google Scholar 

  • Behl C., Davis J. B., Klier F. G., and Schubert D. (1994a) Amyloid beta peptide induces necrosis rather than apoptosis.Brain Res. 645, 253–264.

    Article  CAS  Google Scholar 

  • Behl C., Davis J. B., Lesley R., and Schubert D. (1994b) Hydrogen peroxide mediates amyloid beta protein toxicity.Cell 77, 817–827.

    Article  CAS  Google Scholar 

  • Chartier-Harlin M. C., Crawford F., Houlden H., Warren A., Hughes D., Fidani L., Goate A., Rossor M., Roques P., Hardy J., and Mullan M. (1991) Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene.Nature 353, 844–846.

    Article  CAS  Google Scholar 

  • Citron M., Oltersdorf T., Haass C., McConlogue L., Hung A. Y., Seubert P., Vigo P. C., Lieberburg I., and Selkoe D. J. (1992) Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production.Nature 360, 672–674.

    Article  CAS  Google Scholar 

  • Copani A., Koh J. Y., and Cotman C. W. (1991) Beta-amyloid increases neuronal susceptibility to injury by glucose deprivation.NeuroReport 2, 763–765.

    Article  CAS  Google Scholar 

  • Cotman C. W., Whittemore E. R., Watt J. A., Anderson A. J., and Loo D. T. (1994) Possible role of apoptosis in Alzheimer's disease.Ann. NY Acad. Sci. 747, 36–49.

    Article  CAS  Google Scholar 

  • Ellis R. E., Yuan J. Y., and Horvitz H. R. (1991) Mechanisms and functions of cell death.Annu. Rev. Cell Biol. 7, 663–698.

    Article  CAS  Google Scholar 

  • Estus S., Zaks W. J., Freeman R. S., Gruda M., Bravo R., and Johnson E. J. (1994) Altered gene expression in neurons during programmed cell death: identification of c-jun as necessary for neuronal apoptosis.J. Cell. Biol. 127, 1717–1727.

    Article  CAS  Google Scholar 

  • Forloni G., Chiesa R., Smiroldo S., Verga L., Salmona M., Tagliavini F., and Angeretti N. (1993) Apoptosis mediated neurotoxicity induced by chronic application of beta amyloid fragment 25–35.NeuroReport 4, 523–526.

    Article  CAS  Google Scholar 

  • Freeman R. S., Estus S., Horigome K., and Johnson E. J. (1993) Cell death genes in invertebrates and (maybe) vertebrates.Curr. Opinion Neurobiol. 3, 25–31.

    Article  CAS  Google Scholar 

  • Games D., Adams D., Alessandrini R., Barbour R., Berthelette P., Blackwell C., Carr T., Clemens J., Donaldson T., Gillespie F., et al. (1995) Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein.Nature 373, 523–527.

    Article  CAS  Google Scholar 

  • Gavrieli Y., Sherman Y., and Ben S. S. (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.J. Cell. Biol. 119, 493–501.

    Article  CAS  Google Scholar 

  • Goate A., Chartier-Harlin M. C., Mullan M., Brown J., Crawford F., Fidani L., Giuffra L., Haynes A., Irving N., James L., et al. (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.Nature 349, 704–706.

    Article  CAS  Google Scholar 

  • Greenlund L. J., Deckwerth T. L., and Johnson E. J. (1995) Superoxide dismutase delays neuronal apoptosis: a role for reactive oxygen species in programmed neuronal death.Neuron 14, 303–315.

    Article  CAS  Google Scholar 

  • Hensley K., Carney J. M., Mattson M. P., Aksenova M., Harris M., Wu J. F., Floyd R. A., and Butterfield D. A. (1994) A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease.Proc. Natl. Acad. Sci. USA 91, 3270–3274.

    Article  CAS  Google Scholar 

  • Higgins L. S., Rodems J. M., Catalano R., Quon D., and Cordell B. (1995) Early Alzheimer disease-like histopathology increases in frequency with age in mice transgenic for beta-APP751.Proc. Natl. Acad. Sci. USA 92, 4402–4406.

    Article  CAS  Google Scholar 

  • Kang J., Lemaire H. G., Unterbeck A., Salbaum J. M., Masters C. L., Grzeschik K. H., Multhaup G., Beyreuther K., and Muller H. B. (1987) The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor.Nature 325, 733–736.

    Article  CAS  Google Scholar 

  • Koh J. Y., Yang L. L., and Cotman C. W. (1990) Beta-amyloid protein increases the vulnerability of cultured cortical neurons to excitotoxic damage.Brain Res. 533, 315–320.

    Article  CAS  Google Scholar 

  • LaFerla F. M., Tinkle B. T., Bieberich C. J., Haudenschild C. C., and Jay G. (1995) The Alzheimer's A beta peptide induces neurodegeneration and apoptotic cell death in transgenic mice.Nat. Genet. 9, 21–30.

    Article  CAS  Google Scholar 

  • Lassmann H., Bancher C., Breitschopf H., Wegiel J., Bobinski M., Jellinger K., and Wisniewski H. M. (1995) Cell death in Alzheimer's disease evaluated by DNA fragmentation in situ.Acta. Neuropathol. (Berl) 89, 35–41.

    Article  CAS  Google Scholar 

  • Levy E., Carman M. D., Fernandez M. I., Power M. D., Lieberburg I., van D. S. Bots G. T., Luyendijk W., and Frangione B. (1990) Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type.Science 248, 1124–1126.

    Article  CAS  Google Scholar 

  • Loo D. T., Copani A., Pike C. J., Whittemore E. R., Walencewicz A. J., and Cotman C. W. (1993) Apoptosis is induced by beta-amyloid in cultured central nervous system neurons.Proc. Natl. Acad. Sci. USA 90, 7951–7955.

    Article  CAS  Google Scholar 

  • Mattson M. P., Chen B., Davis D., Bryant K., Lieberburg I., and Rydel R. E. (1992) beta-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity.J. Neurosci. 12, 376–389.

    Article  CAS  Google Scholar 

  • May P. C., Gitter B. D., Waters D. C., Simmons L. K., Becker G. W., Small J. S., and Robison P. M. (1992) beta-Amyloid peptide in vitro toxicity: lot-to-lot variability.Neurobiol. Aging 13, 605–607.

    Article  CAS  Google Scholar 

  • May P. C., Boggs L. N., and Fuson K. S. (1993) Neurotoxicity of human amylin in rat primary hippocampal cultures: similarity to Alzheimer's disease amyloid-β neurotoxicity.J. Neurochem. 61, 2330–2333.

    Article  CAS  Google Scholar 

  • Moran P. M., Higgins L. S., Cordell B., and Moser P. C. (1995) Age-related learning deficits in transgenic mice expressing the 751-amino acid isoform of human beta-amyloid precursor protein.Proc. Natl. Acad. Sci. USA 92, 5341–5345.

    Article  CAS  Google Scholar 

  • Murrell J., Farlow M., Ghetti B., and Benson M. D. (1991) A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease.Science 254, 97–99.

    Article  CAS  Google Scholar 

  • Nicholson D. W., Ali A., Thornberry N. A., Vaillancourt J. P., Ding C. K., Gallant M., Gareau Y., Griffin P. R., Labelle M., Lazebnik Y. A., et al. (1995) Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis.Nature 376, 37–43.

    Article  CAS  Google Scholar 

  • Oppenheim R. W. (1991) Cell death during development of the nervous system.Annu. Rev. Neurosci. 14, 453–501.

    Article  CAS  Google Scholar 

  • Pike C. J., Burdick, D., Walencewicz A. J., Glabe C. G., and Cotman C. W. (1993). Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state.J. Neurosci. 13, 1676–1687.

    Article  CAS  Google Scholar 

  • Pike C. J., Walencewicz W. A., Kosmoski J., Cribbs D. H., Glabe C. G., and Cotman C. W. (1995) Structure-activity analyses of beta-amyloid peptides: contributions of the beta 25–35 region to aggregation and neurotoxicity.J. Neurochem. 64, 253–265.

    Article  CAS  Google Scholar 

  • Schubert D., Behl C., Lesley R., Brack A., Dargusch R., Sagara Y., and Kimura H. (1995) Amyloid peptides are toxic via a common oxidative mechanism.Proc. Natl. Acad. Sci. USA 92, 1989–1993.

    Article  CAS  Google Scholar 

  • Simmons L. K., May P. C., Tomaselli K. J., Rydel R. E., Fuson K. S., Brigham E. F., Wright S., Lieberburg I., Becker G. W., Brems D. N., et al. (1994) Secondary structure of amyloid beta peptide correlates with neurotoxic activity in vitro.Mol. Pharmacol. 45, 373–379.

    CAS  PubMed  Google Scholar 

  • Smale G., Nichols N. R., Brady D. R., Finch C. E., and Horton W. E. J. (1995) Evidence for apoptotic cell death in Alzheimer's disease.Exp. Neurol. 133, 225–230.

    Article  CAS  Google Scholar 

  • Su J. H., Anderson A. J., Cummings B. J., and Cotman C. W. (1994) Immunohistochemical evidence for apoptosis in Alzheimer's disease.NeuroReport 5, 2529–2533.

    Article  CAS  Google Scholar 

  • Suzuki N., Cheung T. T., Cai X. D., Odaka A., Otvos L. J., Eckman C., Golde T. E., and Younkin S. G. (1994) An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants.Science 264, 1336–1340.

    Article  CAS  Google Scholar 

  • Tamaoka A., Odaka A., Ishibashi Y., Usami M., Sahara N., Suzuki N., Nukina N., Mizusawa H., Shoji S., Kanazawa I., et al. (1994) APP717 missense mutation affects the ratio of amyloid beta protein species (A beta 1–42/43 and a beta 1–40) in familial Alzheimer's disease brain.J. Biol. Chem. 269, 32,721–32,724.

    CAS  Google Scholar 

  • Xiong W. C. and Montell C. (1995) Defective glia induce neuronal apoptosis in the repo visual system of Drosophila.Neuron 14, 581–590.

    Article  CAS  Google Scholar 

  • Zhao B., Sisodia S. S., Horton Jr. W. E. Chrest F. J., and Kusiak J. W. (1995a) Altered processing of mutant amyloid precursor proteins induces apoptosis in PC12 cells. manuscript submitted.

  • Zhao B., Sisodia S. S., and Kusiak J. W. (1995b) Altered processing of a mutant amyloid precursor protein in neuronal and endothelial cells.J. Neurosci. Res. 40, 261–268.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Molecular Neurobiology Unit, NIA/Gerontology Research Center, 4940 Eastern Avenue, 21224, Baltimore, MD

    John W. Kusiak, John A. Izzo & Boyu Zhao

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  1. John W. Kusiak
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  2. John A. Izzo
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  3. Boyu Zhao
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Kusiak, J.W., Izzo, J.A. & Zhao, B. Neurodegeneration in Alzheimer disease. Molecular and Chemical Neuropathology 28, 153–162 (1996). https://doi.org/10.1007/BF02815217

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  • DOI: https://doi.org/10.1007/BF02815217

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