Display options
Cite
Portelius E, Andreasson U, Ringman JM, et al. Distinct cerebrospinal fluid amyloid beta peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease. Mol Neurodegener. 2010;5:2doi: 10.1186/1750-1326-5-2.
Portelius, E., Andreasson, U., Ringman, J. M., Buerger, K., Daborg, J., Buchhave, P., Hansson, O., Harmsen, A., Gustavsson, M. K., Hanse, E., Galasko, D., Hampel, H., Blennow, K., & Zetterberg, H. (2010). Distinct cerebrospinal fluid amyloid beta peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease. Molecular neurodegeneration, 52. https://doi.org/10.1186/1750-1326-5-2
Portelius, Erik, et al. "Distinct cerebrospinal fluid amyloid beta peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease." Molecular neurodegeneration vol. 5 (2010): 2. doi: https://doi.org/10.1186/1750-1326-5-2
Portelius E, Andreasson U, Ringman JM, Buerger K, Daborg J, Buchhave P, Hansson O, Harmsen A, Gustavsson MK, Hanse E, Galasko D, Hampel H, Blennow K, Zetterberg H. Distinct cerebrospinal fluid amyloid beta peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease. Mol Neurodegener. 2010 Jan 14;5:2. doi: 10.1186/1750-1326-5-2. PMID: 20145736; PMCID: PMC2818651.
Copy Download .nbib Format: NLM
Share it on

Mol Neurodegener. 2010 Jan 14;5:2. doi: 10.1186/1750-1326-5-2.

Distinct cerebrospinal fluid amyloid beta peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease.

Molecular neurodegeneration

Erik Portelius, Ulf Andreasson, John M Ringman, Katharina Buerger, Jonny Daborg, Peder Buchhave, Oskar Hansson, Andreas Harmsen, Mikael K Gustavsson, Eric Hanse, Douglas Galasko, Harald Hampel, Kaj Blennow, Henrik Zetterberg

Affiliations

  1. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.

PMID: 20145736 PMCID: PMC2818651 DOI: 10.1186/1750-1326-5-2

Abstract

BACKGROUND: Alzheimer's disease (AD) is associated with deposition of amyloid beta (Abeta) in the brain, which is reflected by low concentration of the Abeta1-42 peptide in the cerebrospinal fluid (CSF). There are at least 15 additional Abeta peptides in human CSF and their relative abundance pattern is thought to reflect the production and degradation of Abeta. Here, we test the hypothesis that AD is characterized by a specific CSF Abeta isoform pattern that is distinct when comparing sporadic AD (SAD) and familial AD (FAD) due to different mechanisms underlying brain amyloid pathology in the two disease groups.

RESULTS: We measured Abeta isoform concentrations in CSF from 18 patients with SAD, 7 carriers of the FAD-associated presenilin 1 (PSEN1) A431E mutation, 17 healthy controls and 6 patients with depression using immunoprecipitation-mass spectrometry. Low CSF levels of Abeta1-42 and high levels of Abeta1-16 distinguished SAD patients and FAD mutation carriers from healthy controls and depressed patients. SAD and FAD were characterized by similar changes in Abeta1-42 and Abeta1-16, but FAD mutation carriers exhibited very low levels of Abeta1-37, Abeta1-38 and Abeta1-39.

CONCLUSION: SAD patients and PSEN1 A431E mutation carriers are characterized by aberrant CSF Abeta isoform patterns that hold clinically relevant diagnostic information. PSEN1 A431E mutation carriers exhibit low levels of Abeta1-37, Abeta1-38 and Abeta1-39; fragments that are normally produced by gamma-secretase, suggesting that the PSEN1 A431E mutation modulates gamma-secretase cleavage site preference in a disease-promoting manner.

References

  1. J Alzheimers Dis. 2009;16(1):1-14 - PubMed
  2. Expert Rev Proteomics. 2008 Apr;5(2):225-37 - PubMed
  3. Biomark Med. 2007 Jun;1(1):59-78 - PubMed
  4. Hum Mutat. 2006 Jul;27(7):686-95 - PubMed
  5. Neurogenetics. 2006 Nov;7(4):277-9 - PubMed
  6. Neurobiol Aging. 2008 Oct;29(10):1456-65 - PubMed
  7. Neurobiol Aging. 2011 Jun;32(6):1090-8 - PubMed
  8. Int Psychogeriatr. 1997;9 Suppl 1:173-6; discussion 177-8 - PubMed
  9. J Neurochem. 2005 Nov;95(3):834-47 - PubMed
  10. J Biol Chem. 2008 Oct 17;283(42):28176-89 - PubMed
  11. Neurology. 2003 Feb 25;60(4):652-6 - PubMed
  12. Alzheimers Dement. 2008 Jan;4(1):38-48 - PubMed
  13. J Psychiatr Res. 1975 Nov;12(3):189-98 - PubMed
  14. Lancet Neurol. 2003 Oct;2(10):605-13 - PubMed
  15. Ann Neurol. 2006 Mar;59(3):512-9 - PubMed
  16. Neurosci Lett. 2006 Dec 6;409(3):215-9 - PubMed
  17. J Am Chem Soc. 2009 May 13;131(18):6316-7 - PubMed
  18. J Proteome Res. 2007 Nov;6(11):4433-9 - PubMed
  19. Curr Med Chem. 2008;15(8):766-71 - PubMed
  20. Neurology. 2008 Jul 8;71(2):85-92 - PubMed
  21. Neurogenetics. 2006 Jul;7(3):195-200 - PubMed
  22. J Neurosci. 2007 Mar 14;27(11):2866-75 - PubMed
  23. J Neurochem. 2008 Feb;104(3):573-83 - PubMed
  24. Physiol Rev. 2001 Apr;81(2):741-66 - PubMed
  25. Lancet. 2006 Jul 29;368(9533):387-403 - PubMed
  26. J Proteome Res. 2006 Apr;5(4):1010-6 - PubMed
  27. Neurology. 1984 Jul;34(7):939-44 - PubMed
  28. J Neurosci. 2008 Apr 16;28(16):4231-7 - PubMed
  29. J Neurochem. 2006 Feb;96(3):732-42 - PubMed

Publication Types