Display options
Cite
Shiwany NA, Xie J, Guo Q. Cortical neurons transgenic for human Abeta40 or Abeta42 have similar vulnerability to apoptosis despite their different amyloidogenic properties. Int J Clin Exp Pathol. 2008;2(4):339-52
Shiwany, N. A., Xie, J., & Guo, Q. (2009). Cortical neurons transgenic for human Abeta40 or Abeta42 have similar vulnerability to apoptosis despite their different amyloidogenic properties. International journal of clinical and experimental pathology, 2(4), 339-52.
Shiwany, Najeeb A, et al. "Cortical neurons transgenic for human Abeta40 or Abeta42 have similar vulnerability to apoptosis despite their different amyloidogenic properties." International journal of clinical and experimental pathology vol. 2,4 (2009): 339-52.
Shiwany NA, Xie J, Guo Q. Cortical neurons transgenic for human Abeta40 or Abeta42 have similar vulnerability to apoptosis despite their different amyloidogenic properties. Int J Clin Exp Pathol. 2009;2(4):339-52. Epub 2008 Nov 26. PMID: 19158991; PMCID: PMC2615591.
Copy Download .nbib Format: NLM
Share it on

Int J Clin Exp Pathol. 2009;2(4):339-52. Epub 2008 Nov 26.

Cortical neurons transgenic for human Abeta40 or Abeta42 have similar vulnerability to apoptosis despite their different amyloidogenic properties.

International journal of clinical and experimental pathology

Najeeb A Shiwany, Jun Xie, Qing Guo

Affiliations

  1. Department of Physiology, University of Oklahoma Health Sciences Center Oklahoma City, OK, USA. [email protected], [email protected]

PMID: 19158991 PMCID: PMC2615591

Abstract

Alzheimer's disease (AD) is a leading cause of chronic dementia in the United States. Its incidence is increasing with an attendant increase in associated health care costs. Amyloid beta peptide (Abeta; a 39-42 amino acid molecule) is the major component of senile plaques, the hallmark lesion of AD. The toxic mechanism of Abeta peptides has not been well characterized. Specifically, the impact of Abeta1-40 (Abeta40) and its slightly longer counterpart fragment, Abeta1-42 (Abeta42), is not clearly understood. It has been suggested that, while Abeta40 might play a more physiologically relevant role, Abeta42 is likely the key amyloidogenic fragment leading to amyloid deposition in the form of plaques in AD, a pivotal process in Alzheimer's pathology. This notion was further supported by a recent study employing transgenic mouse models that expressed either Abeta40 or Abeta42 in the absence of human amyloid beta protein precursor (APP) overexpression. It was found that mice expressing Abeta42, but not Abeta40, developed compact amyloid plaques, congophilic amyloid angiopathy, and diffuse Abeta deposits. Since neuronal loss is one of the hallmark features in AD pathology, we hypothesize that cortical neurons from these two strains of transgenic mice for Abeta might show different vulnerability to cell death induced by classical inducers of apoptosis, such as trophic factor withdrawal (TFW). Contrary to our expectations, we found that, while overexpression of either Abeta40 or 42 significantly increased the vulnerability of primary cortical neurons to WFT-induced cell death, there was no significant difference between the two transgenic lines. Mitochondrial dysfunction, levels of oxidative stress, caspase activation and nuclear fragmentation are increased to about the same extent by both Abeta species in transgenic neurons. We conclude that Abeta40 or Abeta42 induce similar levels of neurotoxicity following TFW in these transgenic mice despite the difference in their amyloidogenic properties.

Keywords: Alzheimer's disease; amyloid beta-peptide; cell death; cortical neurons; transgenic mouse model; trophic factor withdrawal

References

  1. Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):715-20 - PubMed
  2. Neuron. 2005 Jul 21;47(2):191-199 - PubMed
  3. J Clin Psychiatry. 2003;64 Suppl 9:7-10 - PubMed
  4. J Neurosci. 2001 May 1;21(9):3017-23 - PubMed
  5. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10540-3 - PubMed
  6. Hum Mol Genet. 2006 May 1;15(9):1437-49 - PubMed
  7. Neurology. 1994 Jun;44(6):1086-90 - PubMed
  8. Nat Med. 2000 Apr;6(4):397-404 - PubMed
  9. Science. 1989 Jul 28;245(4916):417-20 - PubMed
  10. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7611-5 - PubMed
  11. Neurosci Lett. 1989 Dec 15;107(1-3):341-6 - PubMed
  12. J Neurol Sci. 1970 Sep;11(3):205-42 - PubMed
  13. Sci Aging Knowledge Environ. 2006 Mar 08;2006(6):re1 - PubMed
  14. Brain Res. 1997 Jan 2;744(1):7-14 - PubMed
  15. Mol Neurobiol. 1995 Feb;10(1):19-45 - PubMed
  16. Brain Res. 2007 Mar 2;1135(1):12-21 - PubMed
  17. Proc Natl Acad Sci U S A. 1980 Feb;77(2):990-4 - PubMed
  18. Brain Res Brain Res Rev. 2005 Nov;49(3):618-32 - PubMed
  19. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8729-32 - PubMed
  20. Biophys J. 1996 Jan;70(1):296-304 - PubMed
  21. Pharmacol Rev. 2002 Sep;54(3):469-525 - PubMed
  22. J Neurosci Res. 1997 Jan 15;47(2):216-23 - PubMed
  23. J Neurochem. 1997 May;68(5):1870-81 - PubMed
  24. Cell. 1999 Apr 30;97(3):395-406 - PubMed
  25. Science. 1994 May 27;264(5163):1336-40 - PubMed
  26. Neurology. 1990 Aug;40(8):1302-3 - PubMed
  27. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):567-71 - PubMed
  28. Brain Res. 1992 May 8;579(2):333-6 - PubMed
  29. Neurobiol Aging. 1994;15 Suppl 2:S187-9 - PubMed
  30. Med Hypotheses. 2004;63(1):8-20 - PubMed
  31. Biochem Pharmacol. 1999 Jun 15;57(12):1361-5 - PubMed
  32. Trends Neurosci. 1997 Feb;20(2):67-72 - PubMed
  33. J Gen Physiol. 2006 Dec;128(6):637-47 - PubMed
  34. Nat Med. 1998 Aug;4(8):957-62 - PubMed
  35. Trends Biochem Sci. 2001 Jun;26(6):390-7 - PubMed
  36. Brain Res. 1997 Jul 11;762(1-2):144-52 - PubMed
  37. Curr Opin Neurol. 1996 Aug;9(4):254-9 - PubMed
  38. Nat Rev Neurosci. 2002 Nov;3(11):862-72 - PubMed
  39. J Neurosci Res. 1990 Jun;26(2):224-32 - PubMed
  40. Neuron. 1995 Apr;14(4):879-88 - PubMed
  41. Am J Pathol. 2002 Feb;160(2):409-11 - PubMed
  42. Ann Neurol. 2000 Aug;48(2):148-55 - PubMed
  43. Am J Pathol. 1991 Jun;138(6):1423-35 - PubMed
  44. J Mol Neurosci. 1997 Apr;8(2):75-82 - PubMed
  45. Vision Res. 1997 Dec;37(24):3593-608 - PubMed
  46. J Neurol Sci. 1968 Sep-Oct;7(2):331-56 - PubMed
  47. J Neurosci. 1995 Sep;15(9):6239-49 - PubMed
  48. Cell Death Differ. 2003 Aug;10(8):864-9 - PubMed
  49. Nature. 2004 Aug 5;430(7000):631-9 - PubMed
  50. Drug Discov Today. 2006 Oct;11(19-20):931-8 - PubMed

Publication Types