Quantitative Analysis of β-Amyloid Peptides Expressed in Human Cerebrospinal Fluid by an Improved Method of Antibody-Assisted Time-of-Flight Mass Spectrometry

  • Akira Matsumoto
  • Reiko Matsumoto
  • Kei-ichi Kadoyama
  • Taka-aki Nishimoto
  • Shogo Matsuyama
  • Osamu Midorikawa
Article

Abstract

Establishment of diagnostic measures for early stage Alzheimer’s disease (AD) and mild cognitive impairment (MCI) is of crucial importance. Using surface enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS), antibody-assisted MS of cerebrospinal fluid (CSF) has enabled quantitative analysis of the ratio of β-amyloid (Aβ) peptides, Aβ1-42/Aβ1-40, which has a diagnostic value for AD/MCI. To apply the MS analysis to a far wider range of CSF samples, we have established a method to analyze Aβ peptides expressed in 100 μl CSF samples quantitatively. Pretreatment of CSF samples by limit-filtration to condense peptides, and modified washing procedure using urea as denaturant, Aβ peptides of interest can be assessed with higher sensitivity by five to tenfolds to the original method. This improvement enables quantitative analysis of Aβ species from a residual amount of CSF samples, which will be occasionally obtained in case of lumbar anesthesia prior to operation and spinal tap performed for routine diagnostic purposes. Prevalence of the new procedure as laboratory test, especially among the elderly consulting for neurological clinic, will enhance the number of subjects diagnosed at early stage of AD/MCI.

Keywords

Alzheimer’s disease Mild cognitive impairment Dementia β-Amyloid Cerebrospinal fluid Mass spectrometry ProteinChip™ Bio-marker 

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Akira Matsumoto
    • 1
    • 2
  • Reiko Matsumoto
    • 3
    • 5
  • Kei-ichi Kadoyama
    • 2
  • Taka-aki Nishimoto
    • 2
  • Shogo Matsuyama
    • 2
  • Osamu Midorikawa
    • 4
    • 5
  1. 1.Department of Brain Disease Pathogenesis Research, Translational Research Informatics CenterFoundation for Biomedical Research and InnovationChuo-ku, KobeJapan
  2. 2.Faculty of Pharmaceutical SciencesHImeji-Dokkyo UniversityHimejiJapan
  3. 3.Medical CorporationMidorikawa Clinic of NeurologySakyo-ku, KyotoJapan
  4. 4.Kaken General Research InstituteYamashina-ku, KyotoJapan
  5. 5.Department of PathologyKyoto University Graduate School of MedicineSakyo-ku, KyotoJapan

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