Journal of Neurology

, Volume 255, Issue 11, pp 1712–1720

Proteome-based identification of plasma proteins associated with hippocampal metabolism in early Alzheimer’s disease

  • Madhav Thambisetty
  • Abdul Hye
  • Catherine Foy
  • Eileen Daly
  • Amanda Glover
  • Allison Cooper
  • Andrew Simmons
  • Declan Murphy
  • Simon Lovestone
ORIGINAL COMMUNICATION

DOI: 10.1007/s00415-008-0006-8

Cite this article as:
Thambisetty, M., Hye, A., Foy, C. et al. J Neurol (2008) 255: 1712. doi:10.1007/s00415-008-0006-8

Abstract

Background and methods

There is an urgent need for peripheral surrogates of Alzheimer’s disease (AD) that accurately reflect disease state and severity as well as correlate with key features of its neuropathology. The aim of this study was to identify plasma proteins associated with known in vivo markers of disease activity. In an earlier proteomic study of plasma, we discovered a panel of 15 proteins that were differentially expressed in AD and further validated complement factor-H (CFH) and alpha-2-macroglobulin (A2M) as AD-specific plasma biomarkers. In the present study, we extended these findings by testing the associations of these plasma proteins with neuro-imaging measures of disease progression in AD. We combined 1H-magnetic resonance spectroscopy of the hippocampus and MRI-based hippocampal volumetry with proteomic analysis of plasma in early AD and mild cognitive impairment (MCI) to achieve this goal. Using 1H-magnetic resonance spectroscopy, we derived estimates of the hippocampal metabolite ratio N-acetylaspartate/myo-inositol (NAA/mI), a biochemical measure that is associated with cognitive decline in early AD. We also undertook a proteomic analysis of plasma in these individuals using two-dimensional gel electrophoresis (2DGE).

Results

We observed that two plasma proteins previously shown to be differentially expressed in AD, complement factor-H (CFH) and alpha-2-macroglobulin (A2M) showed significant positive correlations with hippocampal NAA/mI ratio in AD.

Conclusions

The association of plasma CFH and A2M with hippocampal NAA/mI in this cohort of AD subjects suggests that these proteins may reflect disease progression in early AD. These findings warrant validation in large population-based datasets.

Key words

Alzheimer’s disease proteomicsN-acetylaspartate/myo-inositolcomplement factor-Halpha-2-macroglobulin

Copyright information

© Springer 2008

Authors and Affiliations

  • Madhav Thambisetty
    • 1
    • 2
    • 6
  • Abdul Hye
    • 3
  • Catherine Foy
    • 1
  • Eileen Daly
    • 4
  • Amanda Glover
    • 5
  • Allison Cooper
    • 5
  • Andrew Simmons
    • 2
    • 5
  • Declan Murphy
    • 2
    • 4
  • Simon Lovestone
    • 1
    • 2
    • 7
  1. 1.King’s College London, MRC Centre for Neurodegeneration ResearchInstitute of PsychiatryLondonUK
  2. 2.NIHR Biomedical Research Centre for Mental HealthSouth London and Maudsley NHS TrustLondonUK
  3. 3.Proteome Sciences plcInstitute of PsychiatryLondonUK
  4. 4.King’s College London, Section of Brain Maturation, Dept. of Psychological MedicineLondonUK
  5. 5.King’s College London, Institute of Psychiatry, Neuroimaging Research GroupLondonUK
  6. 6.National Institute on Aging (NIA)National Institutes of Health (NIH)BethesdaUSA
  7. 7.Section of Old Age Psychiatry, MRC Centre for NeurodegenerationResearch Institute of PsychiatryLondonUK