Proteome-based plasma markers of brain amyloid-β deposition in non-demented older individuals

Madhav Thambisetty, Romina Tripaldi, Joanna Riddoch-Contreras, Abdul Hye, Yang An, James Campbell, Jitka Sojkova, Anna Kinsey, Steven Lynham, Yun Zhou, Luigi Ferrucci, Dean Foster Wong, Simon Lovestone, Susan M. Resnick

Research output: Contribution to journalArticle

Abstract

Blood-based markers reflecting core pathological features of Alzheimer's disease (AD) in pre-symptomatic individuals are likely to accelerate the development of disease-modifying treatments. Our aim was to discover plasma proteins associated with brain amyloid-β (Aβ) burden in non-demented older individuals. We performed discovery-phase experiments using two dimensional gel electrophoresis (2DGE) and mass spectrometry-based proteomic analysis of plasma in combination with 11C-PiB PET imaging of the brain in samples collected 10 years prior to the PET scans. Confirmatory studies used ELISA assays in a separate set of blood samples obtained within a year of the PET scans. We observed that a panel of 18 2DGE plasma protein spots effectively discriminated between individuals with high and low brain Aβ. Mass spectrometry identified these proteins, many of which have established roles in Aβ clearance, including a strong signal from apolipoprotein-E (ApoE). In validation-phase studies, we observed a strong association between plasma ApoE concentration and Aβ burden in the medial temporal lobe. Targeted voxel-based analysis localized this association to the hippocampus and entorhinal cortex. APOE ε4 carriers also showed greater Aβ levels in several brain regions relative to ε4 non-carriers. These results suggest that both peripheral concentration of ApoE protein and APOE genotype are related to early neuropathological changes in brain regions vulnerable to AD pathology even in the non-demented elderly. Our strategy combining proteomics with {\it in vivo} brain amyloid imaging holds promise for the discovery of biologically relevant peripheral markers in those at risk for AD.

Original languageEnglish (US)
Pages (from-to)1099-1109
Number of pages11
JournalJournal of Alzheimer's Disease
Volume22
Issue number4
DOIs
StatePublished - 2010

Fingerprint

Proteome
Amyloid
Apolipoproteins E
Alzheimer Disease
Brain
Neuroimaging
Positron-Emission Tomography
Proteomics
Blood Proteins
Mass Spectrometry
Apolipoproteins A
Entorhinal Cortex
Validation Studies
Electrophoresis, Gel, Two-Dimensional
Temporal Lobe
Hippocampus
Proteins
Enzyme-Linked Immunosorbent Assay
Genotype
Pathology

Keywords

  • Alzheimer's disease
  • amyloid-β
  • biomarker
  • brain
  • plasma
  • proteomics

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

Cite this

Thambisetty, M., Tripaldi, R., Riddoch-Contreras, J., Hye, A., An, Y., Campbell, J., ... Resnick, S. M. (2010). Proteome-based plasma markers of brain amyloid-β deposition in non-demented older individuals. Journal of Alzheimer's Disease, 22(4), 1099-1109. https://doi.org/10.3233/JAD-2010-101350

Proteome-based plasma markers of brain amyloid-β deposition in non-demented older individuals. / Thambisetty, Madhav; Tripaldi, Romina; Riddoch-Contreras, Joanna; Hye, Abdul; An, Yang; Campbell, James; Sojkova, Jitka; Kinsey, Anna; Lynham, Steven; Zhou, Yun; Ferrucci, Luigi; Wong, Dean Foster; Lovestone, Simon; Resnick, Susan M.

In: Journal of Alzheimer's Disease, Vol. 22, No. 4, 2010, p. 1099-1109.

Research output: Contribution to journalArticle

Thambisetty, M, Tripaldi, R, Riddoch-Contreras, J, Hye, A, An, Y, Campbell, J, Sojkova, J, Kinsey, A, Lynham, S, Zhou, Y, Ferrucci, L, Wong, DF, Lovestone, S & Resnick, SM 2010, 'Proteome-based plasma markers of brain amyloid-β deposition in non-demented older individuals', Journal of Alzheimer's Disease, vol. 22, no. 4, pp. 1099-1109. https://doi.org/10.3233/JAD-2010-101350
Thambisetty, Madhav ; Tripaldi, Romina ; Riddoch-Contreras, Joanna ; Hye, Abdul ; An, Yang ; Campbell, James ; Sojkova, Jitka ; Kinsey, Anna ; Lynham, Steven ; Zhou, Yun ; Ferrucci, Luigi ; Wong, Dean Foster ; Lovestone, Simon ; Resnick, Susan M. / Proteome-based plasma markers of brain amyloid-β deposition in non-demented older individuals. In: Journal of Alzheimer's Disease. 2010 ; Vol. 22, No. 4. pp. 1099-1109.
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