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research
Proteome-based plasma biomarkers for Alzheimer's disease
Authors
A. Hye
Aliferis
+61 more
Armstrong
Baird
Bauer
Bertram
Biroccio
Blennow
C. E. Shaw
C. Foy
C. Hooper
Cucullo
D'Andrea
DeKosky
Edwards
Esparza-Gordillo
F. Rijsdijk
Finehout
G. Hamilton
H. L. Byers
Hageman
Haines
Hampel
Hampel
Hampel
Irizarry
J. Campbell
J. Powell
Johnson
Klaver
Liu
Loeffler
Lopez
M. Causevic
M. Poppe
M. Thambisetty
M. Ward
Mattila
Mehta
Mullins
N. Archer
Nath
Newsome
P. Sham
R. G. Brown
Reisberg
Rodriguez de Cordoba
S. Banner
S. J. Tabrizi
S. Lovestone
S. Lynham
Scacchi
Strauss
Strohmeyer
Strohmeyer
Sunderland
Szafranski
Tam
Yang
Yocum
Zhang
Zipser
Zolotarjova
Publication date
1 January 2006
Publisher
'Oxford University Press (OUP)'
Doi
Cite
Abstract
Alzheimer's disease is a common and devastating disease for which there is no readily available biomarker to aid diagnosis or to monitor disease progression. Biomarkers have been sought in CSF but no previous study has used two-dimensional gel electrophoresis coupled with mass spectrometry to seek biomarkers in peripheral tissue. We performed a case-control study of plasma using this proteomics approach to identify proteins that differ in the disease state relative to aged controls. For discovery-phase proteomics analysis, 50 people with Alzheimer's dementia were recruited through secondary services and 50 normal elderly controls through primary care. For validation purposes a total of 511 subjects with Alzheimer's disease and other neurodegenerative diseases and normal elderly controls were examined. Image analysis of the protein distribution of the gels alone identifies disease cases with 56% sensitivity and 80% specificity. Mass spectrometric analysis of the changes observed in two-dimensional electrophoresis identified a number of proteins previously implicated in the disease pathology, including complement factor H (CFH) precursor and α-2-macroglobulin (α- 2M). Using semi-quantitative immunoblotting, the elevation of CFH and α- 2M was shown to be specific for Alzheimer's disease and to correlate with disease severity although alternative assays would be necessary to improve sensitivity and specificity. These findings suggest that blood may be a rich source for biomarkers of Alzheimer's disease and that CFH, together with other proteins such as α- 2M may be a specific markers of this illness. © 2006 The Author(s).link_to_subscribed_fulltex
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