Skip to main content

Two Hits and You’re Out? A Novel Mechanistic Hypothesis of Alzheimer Disease

  • Conference paper
Advances in Alzheimer’s and Parkinson’s Disease

Part of the book series: Advances in Behavioral Biology ((ABBI,volume 57))

  • 2020 Accesses

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Smith MA. Alzheimer disease. Int Rev Neurobiol 1998;42:1–54

    PubMed  CAS  Google Scholar 

  2. Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 1993;261(5123):921–923

    Article  PubMed  CAS  Google Scholar 

  3. Roses AD. Apolipoprotein E genotyping in the differential diagnosis, not prediction, of Alzheimer's disease. Ann Neurol 1995;38(1):6–14

    Article  PubMed  CAS  Google Scholar 

  4. Trojanowski JQ, Schmidt ML, Shin RW, et al. Altered tau and neurofilament proteins in neuro-degenerative diseases: diagnostic implications for Alzheimer's disease and Lewy body dementias. Brain Pathol 1993;3(1):45–54

    PubMed  CAS  Google Scholar 

  5. Selkoe DJ. Alzheimer's disease: genotypes, phenotypes, and treatments. Science 1997;275(5300):630–631

    Article  PubMed  CAS  Google Scholar 

  6. Hsiao K, Chapman P, Nilsen S, et al. Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 1996;274(5284):99–102

    Article  PubMed  CAS  Google Scholar 

  7. Katzman R. Alzheimer's disease, N Engl J Med1986;314(15):964–973

    Article  PubMed  CAS  Google Scholar 

  8. Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol 1956;11(3):298–300

    PubMed  CAS  Google Scholar 

  9. Smith MA, Taneda S, Richey PL, et al. Advanced Maillard reaction end products are associated with Alzheimer disease pathology. Proc Natl Acad Sci USA 1994;91(12):5710–5714

    Article  PubMed  CAS  Google Scholar 

  10. Smith MA, Kutty RK, Richey PL, et al. Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer's disease. Am J Pathol 1994;145(1):42–47

    PubMed  CAS  Google Scholar 

  11. Smith MA, Rudnicka-Nawrot M, Richey PL, et al. Carbonyl-related posttranslational modification of neurofilament protein in the neurofibrillary pathology of Alzheimer's disease. J Neurochem 1995;64(6):2660–2666

    PubMed  CAS  Google Scholar 

  12. Smith MA, M. Sayre LM, Monnier CM, Perry G. Radical AGEing in Alzheimer's disease. Trends Neurosci 18(4):172–176

    Google Scholar 

  13. Smith MA, Sayre LM, Vitek MP, et al. Early AGEing and Alzheimer's. Nature 1995;374(6520):316

    Article  PubMed  CAS  Google Scholar 

  14. Smith MA, Perry G, Richey PL, et al. Oxidative damage in Alzheimer's. Nature 1996;382(6587):120–121

    Article  PubMed  CAS  Google Scholar 

  15. Smith MA, Siedlak SL, Richey PL, e al. Quantitative solubilization and analysis of insoluble paired helical filaments from Alzheimer disease. Brain Res 1996;717(1-2):99–108

    Article  PubMed  CAS  Google Scholar 

  16. Smith MA, Richey Harris PL, Sayre LM, et al. Widespread peroxynitrite-mediated damage in Alzheimer's disease. J Neurosci 1997;17(8):2653–2657

    PubMed  CAS  Google Scholar 

  17. Smith MA, Harris PL, Sayre LM, Perry G. Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc Natl Acad Sci USA 1997;94(18):9866–9868

    Article  PubMed  CAS  Google Scholar 

  18. Sayre LM, Zelasko DA, Harris PL, et al. 4-Hydroxynonenal-derived advanced lipid peroxidation end products are increased in Alzheimer's disease. J Neurochem 1997;68(5):2092–2097

    PubMed  CAS  Google Scholar 

  19. Nunomura A, Perry G, Pappolla MA, et al. RNA oxidation is a prominent feature of vulnerable neurons in Alzheimer's disease. J Neurosci 1999;19(6):1959–1964

    PubMed  CAS  Google Scholar 

  20. Nunomura A, Perry G, Pappolla MA, et al. Neuronal oxidative stress precedes amyloid-beta deposition in Down syndrome. J Neuropathol Exp Neurol 2000;59(11):1011–1017

    PubMed  CAS  Google Scholar 

  21. Nunomura A, Perry G, Aliev G, et al. Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 2001;60(8):759–767

    PubMed  CAS  Google Scholar 

  22. Perry G, Castellani RJ, Smith MA, et al. Oxidative damage in the olfactory system in Alzheimer's disease. Acta Neuropathol (Berl) 2003;106(6):552–556

    Article  CAS  Google Scholar 

  23. Raina AK, Zhu X, Rottkamp CA, et al. Cyclin' toward dementia: cell cycle abnormalities and abortive oncogenesis in Alzheimer disease. J Neurosci Res 2000;61(2):128–133

    Article  PubMed  CAS  Google Scholar 

  24. Bowser R, Smith MA. Cell cycle proteins in Alzheimer's disease: plenty of wheels but no cycle. J Alzheimers Dis 2002;4(3):249–254

    PubMed  CAS  Google Scholar 

  25. Sayre LM, Perry G, Harris PL, et al. In situ oxidative catalysis by neurofibrillary tangles and senile plaques in Alzheimer's disease: a central role for bound transition metals. J Neurochem 2000;74(1):270–279

    Article  PubMed  CAS  Google Scholar 

  26. Oteiza PI. A mechanism for the stimulatory effect of aluminum on iron-induced lipid peroxidation. Arch Biochem Biophys 1994;308(2):374–379

    Article  PubMed  Google Scholar 

  27. Good PF, Perl DP, Bierer LM, Schmeidler J. Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer's disease: a laser microprobe (LAMMA) study. Ann Neurol 1992;31(3):286–292

    Article  PubMed  CAS  Google Scholar 

  28. Cras P, Kawai M, Siedlak S, et al. Neuronal and microglial involvement in beta-amyloid protein deposition in Alzheimer's disease. Am J Pathol 1990;137(2):241–246

    PubMed  CAS  Google Scholar 

  29. Colton CA, Gilbert DL. Production of superoxide anions by a CNS macrophage, the microglia. FEBS Lett 1987;223(2):284–288

    Article  PubMed  CAS  Google Scholar 

  30. Good PF, Werner P, Hsu A, et al. Evidence of neuronal oxidative damage in Alzheimer's disease. Am J Pathol 1996;149(1):21–28

    PubMed  CAS  Google Scholar 

  31. Butterfield DA, Hensley K, Harris M, et al. beta-Amyloid peptide free radical fragments initiate synaptosomal lipoperoxidation in a sequence-specific fashion: implications to Alzheimer's disease. Biochem Biophys Res Commun 1994;200(2):710–715

    Article  PubMed  CAS  Google Scholar 

  32. Butterfield DA, Bush AI. Alzheimer's amyloid beta-peptide (1-42): involvement of methionine residue 35 in the oxidative stress and neurotoxicity properties of this peptide. Neurobiol Aging 2004;25(5):563–568

    Article  PubMed  CAS  Google Scholar 

  33. Hensley K, Carney JM, Mattson MP, et al. A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc Natl Acad Sci U S A 1994;91(8):3270–3274

    Article  PubMed  CAS  Google Scholar 

  34. Sayre LM, Zagorski MG, Surewicz WK, et al. Mechanisms of neurotoxicity associated with amyloid beta deposition and the role of free radicals in the pathogenesis of Alzheimer's disease: a critical appraisal. Chem Res Toxicol 1997;10(5):518-526

    Article  PubMed  CAS  Google Scholar 

  35. Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes 1991;40(4):405-412

    Article  PubMed  CAS  Google Scholar 

  36. Yan SD, Yan SF, Chen X, et al. Non-enzymatically glycated tau in Alzheimer's disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid beta-peptide. Nat Med 1995;1(7):693–699

    Article  PubMed  CAS  Google Scholar 

  37. Yan SD, Chen X, Schmidt AM, et al. Glycated tau protein in Alzheimer disease: a mechanism for induction of oxidant stress. Proc Natl Acad Sci USA 1994;91(16):7787–7791

    Article  PubMed  CAS  Google Scholar 

  38. Munch G, Kuhla B, Luth HJ, et al. Anti-AGEing defences against Alzheimer's disease. Biochem Soc Trans 2003;31(Pt 6):1397–1399

    PubMed  CAS  Google Scholar 

  39. El Khoury J, Hickman SE, Thomas CA, et al. Scavenger receptor-mediated adhesion of microglia to beta-amyloid fibrils. Nature 1996;382(6593):716–719

    Article  PubMed  CAS  Google Scholar 

  40. Yan SD, Chen X, Fu J, et al. RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Nature 382(6593):685–691

    Google Scholar 

  41. Davis RE, Miller S, Herrnstadt C, et al. Mutations in mitochondrial cytochrome c oxidase genes segregate with late-onset Alzheimer disease. Proc Natl Acad Sci USA 1997;94(9):4526–4531

    Article  PubMed  CAS  Google Scholar 

  42. Hirai K, Aliev G, Nunomura A, et al. Mitochondrial abnormalities in Alzheimer's disease. J Neurosci 2001;21(9):3017–3023

    PubMed  CAS  Google Scholar 

  43. Coskun PE, Beal MF, Wallace DC. Alzheimer's brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication. Proc Natl Acad Sci U S A 2004;101(29):10726–10731

    Article  PubMed  CAS  Google Scholar 

  44. Lustbader JW, Cirilli M, Lin C, et al. ABAD directly links Aβ to mitochondrial toxicity in Alzheimer's disease. Science 2004;304(5669):448-452

    Article  PubMed  CAS  Google Scholar 

  45. Manczak M, Park BS, Jung Y, Reddy PH. Differential expression of oxidative phosphorylation genes in patients with Alzheimer's disease: implications for early mitochondrial dysfunction and oxidative damage. Neuromol Med 2004;5(2):147–162

    Article  CAS  Google Scholar 

  46. Trimmer PA, Keeney PM, Borland MK, et al. Mitochondrial abnormalities in cybrid cell models of sporadic Alzheimer's disease worsen with passage in culture. Neurobiol Dis 2004;15(1):29–39

    Article  PubMed  CAS  Google Scholar 

  47. Williamson KS, Gabbita SP, Mou S, et al. The nitration product 5-nitro-gamma-tocopherol is increased in the Alzheimer brain. Nitric Oxide 2002;6(2):221–227

    Article  PubMed  CAS  Google Scholar 

  48. Castegna A, Thongboonkerd V, Klein JB, et al. Proteomic identification of nitrated proteins in Alzheimer's disease brain. J Neurochem 2003;85(6):1394–1401

    Article  PubMed  CAS  Google Scholar 

  49. Palmer AM, Burns MA, Selective increase in lipid peroxidation in the inferior temporal cortex in Alzheimer's disease. Brain Res 1994;645(1-2):338–342

    Article  PubMed  CAS  Google Scholar 

  50. Butterfield DA, Drake J, Pocernich C, Castegna A. Evidence of oxidative damage in Alzheimer's disease brain: central role for amyloid beta-peptide. Trends Mol Med 2001;7(12):548–554

    Article  PubMed  CAS  Google Scholar 

  51. Tamaoka A, Miyatake F, Matsuno S, et al. Apolipoprotein E allele-dependent antioxidant activity in brains with Alzheimer's disease. Neurology 2000;54(12):2319–2321

    PubMed  CAS  Google Scholar 

  52. Lovell MA, Ehmann WD, Butler SM, Markesbery WR. Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer's disease. Neurology 1995;45(8):1594–1601

    PubMed  CAS  Google Scholar 

  53. Markesbery WR, Lovell MA, Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer's disease. Neurobiol Aging 1998;19(1):33–36

    Article  PubMed  CAS  Google Scholar 

  54. Guan Z, Wang Y, Cairns NJ, et al. Decrease and structural modifications of phosphatidylethanolamine plasmalogen in the brain with Alzheimer disease. J Neuropathol Exp Neurol 1999;58(7):740–747

    PubMed  CAS  Google Scholar 

  55. Wataya T, Nunomura A, Smith MA, et al. High molecular weight neurofilament proteins are physiological substrates of adduction by the lipid peroxidation product hydroxynonenal. J Biol Chem 2002;277(7):4644–4648

    Article  PubMed  CAS  Google Scholar 

  56. Smith CD, Carney JM, Starke-Reed PE, et al. Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc Natl Acad Sci USA 1991;88(23):10540–10543

    Article  PubMed  CAS  Google Scholar 

  57. Ledesma MD, Bonay P, Colaco C, Avila J. Analysis of microtubule-associated protein tau glycation in paired helical filaments. J Biol Chem 1994;269(34):21614–21619

    PubMed  CAS  Google Scholar 

  58. Vitek MP, Bhattacharya K, Glendening JM, et al. Advanced glycation end products contribute to amyloidosis in Alzheimer disease. Proc Natl Acad Sci USA 1994;91(11):4766–4770

    Article  PubMed  CAS  Google Scholar 

  59. Montine TJ, Amarnath V, Martin ME, et al. E-4-hydroxy-2-nonenal is cytotoxic and cross-links cytoskeletal proteins in P19 neuroglial cultures. Am J Pathol 1996;148(1):89–93

    PubMed  CAS  Google Scholar 

  60. Takeda A, Smith MA, Avila J, et al. In Alzheimer's disease, heme oxygenase is coincident with Alz50, an epitope of tau induced by 4-hydroxy-2-nonenal modification. J Neurochem 2000;75(3):1234–1241

    Article  PubMed  CAS  Google Scholar 

  61. Cras P, Smith MA, Richey PL, et al. Extracellular neurofibrillary tangles reflect neuronal loss and provide further evidence of extensive protein cross-linking in Alzheimer disease. Acta Neuropathol (Berl) 1995;89(4):291–295

    Article  CAS  Google Scholar 

  62. Friguet B, Stadtman ER, Szweda LI, Modification of glucose-6-phosphate dehydrogenase by 4-hydroxy-2-nonenal: formation of cross-linked protein that inhibits the multi-catalytic protease. J Biol Chem 1994;269(34):21639–21643

    PubMed  CAS  Google Scholar 

  63. Perry G, Mulvihill P, Manetto V, et al. Immunocytochemical properties of Alzheimer straight filaments. J Neurosci 1987;7(11):3736–3738

    PubMed  CAS  Google Scholar 

  64. Smith MA, Perry G. Alzheimer disease: an imbalance of proteolytic regulation? Med Hypotheses 1994;42(4):277–279

    Article  PubMed  CAS  Google Scholar 

  65. Galloway PG, Grundke-Iqbal I, Iqbal K, Perry G. Lewy bodies contain epitopes both shared and distinct from Alzheimer neurofibrillary tangles. J Neuropathol Exp Neurol 1988;47(6):654–663

    PubMed  CAS  Google Scholar 

  66. Manetto V, Abdul-Karim FW, Perry G, et al. Selective presence of ubiquitin in intracellular inclusions. Am J Pathol 1989;134(3):505–513

    PubMed  CAS  Google Scholar 

  67. Castellani R, Smith MA, Richey PL, et al. Evidence for oxidative stress in Pick disease and corticobasal degeneration. Brain Res 1995;696(1-2):268–271

    Article  PubMed  CAS  Google Scholar 

  68. Castellani R, Smith MA, Richey PL, Perry G. Glycoxidation and oxidative stress in Parkinson disease and diffuse Lewy body disease. Brain Res 1996;737(1-2):195–200

    Article  PubMed  CAS  Google Scholar 

  69. Castellani RJ, Perry G, Harris PL, et al. Advanced glycation modification of Rosenthal fibers in patients with Alexander disease. Neurosci Lett 1997;231(2):79–82

    Article  PubMed  CAS  Google Scholar 

  70. Pappolla MA, Omar RA, Kim KS, Robakis NK. Immunohistochemical evidence of oxidative [corrected] stress in Alzheimer's disease. Am J Pathol 1992;140(3):621–628

    PubMed  CAS  Google Scholar 

  71. Aksenov MY, Tucker HM, Nair P, et al. The expression of key oxidative stress-handling genes in different brain regions in Alzheimer's disease. J Mol Neurosci 1998;11(2):151–164

    Article  PubMed  CAS  Google Scholar 

  72. Lee SC, Zhao ML, Hirano A, Dickson DW, Inducible nitric oxide synthase immunoreactivity in the Alzheimer disease hippocampus: association with Hirano bodies, neurofibrillary tangles, and senile plaques. J Neuropathol Exp Neurol 1999;58(11):1163–1169

    PubMed  CAS  Google Scholar 

  73. Perry G, Smith MA. Is oxidative damage central to the pathogenesis of Alzheimer disease? Acta Neurol Belg 1998;98(2):175–179

    PubMed  CAS  Google Scholar 

  74. Nunomura A, Chiba S, Lippa CF, et al. Neuronal RNA oxidation is a prominent feature of familial Alzheimer's disease. Neurobiol Dis 2004;17(1):108–113

    Article  PubMed  CAS  Google Scholar 

  75. Pratico D, Uryu K, Leight S, et al. Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. J Neurosci 2001;21(12):4183–4187

    PubMed  CAS  Google Scholar 

  76. Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease: The Alzheimer's Disease Cooperative Study. N Engl J Med 1997;336(17):1216–1222

    Article  PubMed  CAS  Google Scholar 

  77. Stewart WF, Kawas C, Corrada M, Metter EJ. Risk of Alzheimer's disease and duration of NSAID use. Neurology 1997;48(3):626–632

    PubMed  CAS  Google Scholar 

  78. Pratico D, Lee MY V, Trojanowski JQ, et al. Increased F2-isoprostanes in Alzheimer's disease: evidence for enhanced lipid peroxidation in vivo. FASEB J 1998;12(15):1777–1783

    PubMed  CAS  Google Scholar 

  79. Pratico D, Clark CM, Lee VM, et al. Increased 8,12-iso-iPF2alpha-VI in Alzheimer's disease: correlation of a noninvasive index of lipid peroxidation with disease severity. Ann Neurol 2000;48(5):809–812

    Article  PubMed  CAS  Google Scholar 

  80. Pratico D, Clark CM, Liun F, et al. Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. Arch Neurol 2002;59(6):972–976

    Article  PubMed  Google Scholar 

  81. Odetti P, Angelini G, Dapino D, et al. Early glycoxidation damage in brains from Down's syndrome. Biochem Biophys Res Commun 1998;243(3):849–851

    Article  PubMed  CAS  Google Scholar 

  82. Smith MA, Hirai K, Hsiao K, et al. Amyloid-beta deposition in Alzheimer transgenic mice is associated with oxidative stress. J Neurochem 1998;70(5):2212–2215

    Article  PubMed  CAS  Google Scholar 

  83. Grana X, Reddy EP. Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene 1995;11(2):211–219

    PubMed  CAS  Google Scholar 

  84. Sherr CJ. G1 phase progression: cycling on cue. Cell 1994;79(4):551–555

    Article  PubMed  CAS  Google Scholar 

  85. Meikrantz W, Schlegel R. Apoptosis and the cell cycle. J Cell Biochem 1995;58(2):160–174

    Article  PubMed  CAS  Google Scholar 

  86. Smith TW, Lippa CF. Ki-67 immunoreactivity in Alzheimer's disease and other neurodegenerative disorders. J Neuropathol Exp Neurol 1995;54(3):297–303

    Article  PubMed  CAS  Google Scholar 

  87. McShea A, Harris PL, Webster KE, et al. Abnormal expression of the cell cycle regulators P16 and CDK4 in Alzheimer's disease. Am J Pathol 1997;150(6):1933–1939

    PubMed  CAS  Google Scholar 

  88. Nagy Z, Esiri MM, Smith AD. Expression of cell division markers in the hippocampus in Alzheimer's disease and other neurodegenerative conditions. Acta Neuropathol (Berl) 1997;93(3):294–300

    Article  CAS  Google Scholar 

  89. Nagy Z, Esiri MM, Cato AM, Smith AD. Cell cycle markers in the hippocampus in Alzheimer's disease. Acta Neuropathol (Berl) 1997;94(1):6–15

    Article  CAS  Google Scholar 

  90. Harris PL, Zhu X, Pamies C, et al. Neuronal polo-like kinase in Alzheimer disease indicates cell cycle changes. Neurobiol Aging 2000;21(6):837–841

    Article  PubMed  CAS  Google Scholar 

  91. Yang Y, Geldmacher DS, Herrup K. DNA replication precedes neuronal cell death in Alzheimer's disease. J Neurosci 2001;21(8):2661–2668

    PubMed  CAS  Google Scholar 

  92. Ogawa O, Lee HG, Zhu X, et al. Increased p27, an essential component of cell cycle control, in Alzheimer's disease. Aging Cell 2003;2(2):105–110

    Article  PubMed  CAS  Google Scholar 

  93. Ogawa O, Zhu X, H. G. Lee HG, et al. Ectopic localization of phosphorylated histone H3 in Alzheimer's disease: a mitotic catastrophe? Acta Neuropathol (Berl) 2003;105(5):524–528

    CAS  Google Scholar 

  94. Zhu X, McShea A, Harris PL, et al. Elevated expression of a regulator of the G2/M phase of the cell cycle, neuronal CIP-1-associated regulator of cyclin B, in Alzheimer's disease. J Neurosci Res 2004;75(5):698–703

    Article  PubMed  CAS  Google Scholar 

  95. Zhu X, Raina AK, Smith MA. Cell cycle events in neurons: proliferation or death? Am J Pathol 1999;155(2):327–329

    PubMed  CAS  Google Scholar 

  96. Vincent I, Jicha G, Rosado M, Dickson DW. Aberrant expression of mitotic cdc2/cyclin B1 kinase in degenerating neurons of Alzheimer's disease brain. J Neurosci 1997;17(10):3588–3598

    PubMed  CAS  Google Scholar 

  97. Busser J, Geldmacher DS, Herrup K. Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer's disease brain. J Neurosci 1998;18(8):2801–2807

    PubMed  CAS  Google Scholar 

  98. Zhu X, Rottkamp CA, Raina AK, et al. Neuronal CDK7 in hippocampus is related to aging and Alzheimer disease. Neurobiol Aging 2000;21(6):807–813

    Article  PubMed  CAS  Google Scholar 

  99. Vincent I, Zheng JH, Dickson DW, et al. Mitotic phosphoepitopes precede paired helical filaments in Alzheimer's disease. Neurobiol Aging 1998;19(4):287–296

    Article  PubMed  CAS  Google Scholar 

  100. Yang Y, Mufson EJ, Herrup K. Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer's disease. J Neurosci 2003;23(7):2557–2563

    PubMed  CAS  Google Scholar 

  101. Zhu X, Raina AK, Perry G, Smith MA. Alzheimer's disease: the two-hit hypothesis. Lancet Neurol 2004;3(4):219–226

    Article  PubMed  CAS  Google Scholar 

  102. Perry G, Nunomura A, Smith MA. A suicide note from Alzheimer disease neurons? Nat Med 1998;4(8):897–898

    Article  PubMed  CAS  Google Scholar 

  103. Perry G, Zhu X, Smith MA. Do neurons have a choice in death? Am J Pathol 2001;158(1):1–2

    PubMed  CAS  Google Scholar 

  104. Keyse SM, Tyrrell RM. Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. Proc Natl Acad Sci U S A 1989;86(1):99–103

    Article  PubMed  CAS  Google Scholar 

  105. Rushmore TH, King RG, Paulson KE, Pickett DB. Regulation of glutathione S-transferase Ya subunit gene expression: identification of a unique xenobiotic-responsive element controlling inducible expression by planar aromatic compounds. Proc Natl Acad Sci U S A 1990;87(10):3826–3830

    Article  PubMed  CAS  Google Scholar 

  106. Davies JM, Lowry CV, Davies KJ. Transient adaptation to oxidative stress in yeast. Arch Biochem Biophys 1995;317(1):1–6

    Article  PubMed  CAS  Google Scholar 

  107. Wiese AG, Pacifici RE, Davies KJ. Transient adaptation of oxidative stress in mammalian cells. Arch Biochem Biophys 1995;318(1):231–240

    Article  PubMed  CAS  Google Scholar 

  108. LeBel CP, Bondy SC. Oxidative damage and cerebral aging. Prog Neurobiol 1992;38(6):601–609

    Article  PubMed  CAS  Google Scholar 

  109. Chao M, Zhu X, Raina AK, et al. Sources contributing to the initiation and propagation of oxidative stress in Alzheimer disease. Proc Indian Natl Sci Acad Part B 2003;69:251–260

    CAS  Google Scholar 

  110. Mattson MP, Chan SL, Duan W. Modification of brain aging and neurodegenerative disorders by genes, diet, and behavior. Physiol Rev 2002;82(3):637–672

    PubMed  CAS  Google Scholar 

  111. Allen SJ, MacGowan SH, Treanor JJ, et al. Normal beta-NGF content in Alzheimer's disease cerebral cortex and hippocampus. Neurosci Lett 1991;131(1):135–139

    Article  PubMed  CAS  Google Scholar 

  112. Crutcher KA, Scott SA, Liang S, et al. Detection of NGF-like activity in human brain tissue: increased levels in Alzheimer's disease. J Neurosci 1993;13(6):2540–2550

    PubMed  CAS  Google Scholar 

  113. Connor B, Young D, Lawlor P, et al. Trk receptor alterations in Alzheimer's disease. Brain Res Mol Brain Res 1996;42(1):1–17

    Article  PubMed  CAS  Google Scholar 

  114. Hardy J. Amyloid, the presenilins and Alzheimer's disease. Trends Neurosci 1997;20(4):154–159

    Article  PubMed  CAS  Google Scholar 

  115. Chen Y, McPhie DL, Hirschberg L, Neve RL. The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in neurons. J Biol Chem 2000;275(12):8929–8935

    Article  PubMed  CAS  Google Scholar 

  116. Neve RL, McPhie DL, Chen Y. Alzheimer's disease: a dysfunction of the amyloid precursor protein(1). Brain Res 2000;886(1-2):54–66

    Article  PubMed  CAS  Google Scholar 

  117. Bruni P, Minopoli G, Brancaccio Y, et al. Fe65, a ligand of the Alzheimer's beta-amyloid precursor protein, blocks cell cycle progression by down-regulating thymidylate synthase expression. J Biol Chem 2002;277(38):35481–35488

    Article  PubMed  CAS  Google Scholar 

  118. Schubert D, Cole G, Saitoh Y, Oltersdorf T. Amyloid beta protein precursor is a mitogen. Biochem Biophys Res Commun 1989;162(1):83–88

    Article  PubMed  CAS  Google Scholar 

  119. Milward EA, Papadopoulos R, Fuller SJ, et al. The amyloid protein precursor of Alzheimer's disease is a mediator of the effects of nerve growth factor on neurite outgrowth. Neuron 1992;9(1):129–137

    Article  PubMed  CAS  Google Scholar 

  120. Copani A, Condorelli F, Caruso A, et al. Mitotic signaling by beta-amyloid causes neuronal death. FASEB J 1999;13(15):2225–2234

    PubMed  CAS  Google Scholar 

  121. Hoffmann J, Twiesselmann C, Kummer MP, et al. A possible role for the Alzheimer amyloid precursor protein in the regulation of epidermal basal cell proliferation. Eur J Cell Biol 2000;79(12):905–914

    Article  PubMed  CAS  Google Scholar 

  122. Schmitz A, Tikkanen R, Kirfel G, Herzog V. The biological role of the Alzheimer amyloid precursor protein in epithelial cells. Histochem Cell Biol 2002;117(2):171–180

    Article  PubMed  CAS  Google Scholar 

  123. Eckert A, Steiner B, Marques C, et al. Elevated vulnerability to oxidative stress-induced cell death and activation of caspase-3 by the Swedish amyloid precursor protein mutation. J Neurosci Res 2001;64(2):183–192

    Article  PubMed  CAS  Google Scholar 

  124. Marques CA, Keil U, Bonert A, et al. Neurotoxic mechanisms caused by the Alzheimer's disease-linked Swedish amyloid precursor protein mutation: oxidative stress, caspases, and the JNK pathway. J Biol Chem 2003;278(30):28294–28302

    Article  PubMed  CAS  Google Scholar 

  125. Leutz S, Steiner B, Marques CA, et al. Reduction of trophic support enhances apoptosis in PC12 cells expressing Alzheimer's APP mutation and sensitizes cells to staurosporine-induced cell death. J Mol Neurosci 2002;18(3):189–201

    Article  PubMed  CAS  Google Scholar 

  126. Xu X, Yang D, Wyss-Coray T, et al. Wild-type but not Alzheimer-mutant amyloid precursor protein confers resistance against p53-mediated apoptosis. Proc Natl Acad Sci U S A 1999;96(13):7547–7552

    Article  PubMed  CAS  Google Scholar 

  127. Koistinaho M, Kettunen MI, Goldsteins G, et al. Beta-amyloid precursor protein transgenic mice that harbor diffuse A beta deposits but do not form plaques show increased ischemic vulnerability: role of inflammation. Proc Natl Acad Sci USA 2002;99(3):1610–1615

    Article  PubMed  CAS  Google Scholar 

  128. Nakagawa Y, Nakamura M, McIntosh TK, et al. Traumatic brain injury in young, amyloid-beta peptide overexpressing transgenic mice induces marked ipsilateral hippocampal atrophy and diminished Aβ deposition during aging. J Comp Neurol 1999;411(3):390–398

    Article  PubMed  CAS  Google Scholar 

  129. Janicki SM, Monteiro MJ. Presenilin overexpression arrests cells in the G1 phase of the cell cycle: arrest potentiated by the Alzheimer's disease PS2(N141I) mutant. Am J Pathol 1999;155(1):135–144

    PubMed  CAS  Google Scholar 

  130. Janicki SM, Stabler SM, Monteiro MJ. Familial Alzheimer's disease presenilin-1 mutants potentiate cell cycle arrest. Neurobiol Aging 2000;21(6):829–836

    Article  PubMed  CAS  Google Scholar 

  131. Prat MI, Adamo AM, Gonzalez SA, et al. Presenilin 1 overexpressions in Chinese hamster ovary (CHO) cells decreases the phosphorylation of retinoblastoma protein: relevance for neurodegeneration. Neurosci Lett 2002;326(1):9–12

    Article  PubMed  CAS  Google Scholar 

  132. Soriani M, Pietraforte D, Minetti M. Antioxidant potential of anaerobic human plasma: role of serum albumin and thiols as scavengers of carbon radicals. Arch Biochem Biophys 1994;312(1):180–188

    Article  PubMed  CAS  Google Scholar 

  133. Yuasa S, Nakajima M, Aizawa H, et al. Impaired cell cycle control of neuronal precursor cells in the neocortical primordium of presenilin-1-deficient mice. J Neurosci Res 2002;70(3):501–513.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science+Business Media, LLC

About this paper

Cite this paper

Zhu, X., Perry, G., Smith, M.A. (2008). Two Hits and You’re Out? A Novel Mechanistic Hypothesis of Alzheimer Disease. In: Fisher, A., Memo, M., Stocchi, F., Hanin, I. (eds) Advances in Alzheimer’s and Parkinson’s Disease. Advances in Behavioral Biology, vol 57. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-72076-0_19

Download citation

Publish with us

Policies and ethics