Proteomic identification and early validation of complement 1 inhibitor and pigment epithelium-derived factor: Two novel biomarkers of Alzheimer's disease in human plasma.
Emerging disease modifying therapeutic strategies for Alzheimer's disease (AD) have generated a critical need for biomarkers of early stage disease. Here, we describe the identification and assessment of a number of candidate biomarkers in patients with mild to moderate probable AD. Plasma from 47 probable Alzheimer's patients and 47 matched controls were analysed by proteomics to define a significant number of proteins whose expression appeared to be associated with AD. These were compared to a similar proteomic comparison of a mouse transgenic model of amyloidosis, which showed encouraging overlap with the human data. From these studies a prioritised list of 31 proteins were then analysed by immunoassay and/or functional assay in the same human cohort to verify the changes observed. Eight proteins continued to show significance by either immunoassay or functional assay in the human plasma and these were tested in a further set of 100 probable AD patients and 100 controls from the original cohort. From our data it appeared that two proteins, serpin F1 (pigment epithelium-derived factor) and complement C1 inhibitor are down-regulated in plasma from AD patients.
GlaxoSmithKline, New Frontiers Science Park, Harlow, UK. paul.cutler@gsk.com.
Paul
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Cutler
Emma L
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Akuffo
Wanda M
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Bodnar
Deborah M
DM
Briggs
John B
JB
Davis
Christine M
CM
Debouck
Steven M
SM
Fox
Rachel A
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Gibson
Darren A
DA
Gormley
Joanna D
JD
Holbrook
A Jacqueline
AJ
Hunter
Emma E
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Kinsey
Rabinder
R
Prinjha
Jill C
JC
Richardson
Allen D
AD
Roses
Marjorie A
MA
Smith
Nikos
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Tsokanas
David R
DR
Willé
Wen
W
Wu
John W
JW
Yates
Israel S
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Gloger