The discovery and early validation of novel plasma biomarkers in mild-to-moderate Alzheimer's disease patients responding to treatment with rosiglitazone.

Published

Journal Article

Recent advances in clinical, pathological and neuroscience studies have identified disease-modifying therapeutic approaches for Alzheimer's disease that are now in clinical trials. This has highlighted the need for reliable and convenient biomarkers for both early disease diagnosis and a rapid signal of drug efficacy. We describe the identification and assessment of a number of candidate biomarkers in patients with Alzheimer's disease and the correlation of those biomarkers with rosiglitazone therapeutic efficacy, as represented by a change in the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog). Plasma from 41 patients with Alzheimer's disease were analysed by open platform proteomics at baseline and after receiving 8 mg rosiglitazone for 24 weeks. From a comparison of protein expression following treatment with rosiglitazone, 97 proteins were observed to be differentially expressed with a p-value<0.01. From this analysis and comparison to recently published data from our laboratory, a prioritized list of 10 proteins were analysed by immunoassay and/or functional assay in a wider set of samples from the same clinical study, representing a rosiglitazone dose response, in order to verify the changes observed. A number of these proteins appeared to show a correlation with change in ADAS-Cog at the higher treatment doses compared with the placebo. Alpha-2-macroglobulin, complement C1 inhibitor, complement factor H and apolipoprotein E expression showed a correlation with ADAS-Cog score at the higher doses (4 mg and 8 mg). These results are discussed in light of the pathology and other recently published data.

Full Text

Duke Authors

Cited Authors

  • Akuffo, EL; Davis, JB; Fox, SM; Gloger, IS; Hosford, D; Kinsey, EE; Jones, NA; Nock, CM; Roses, AD; Saunders, AM; Skehel, JM; Smith, MA; Cutler, P

Published Date

  • September 2008

Published In

Volume / Issue

  • 13 / 6

Start / End Page

  • 618 - 636

PubMed ID

  • 18830857

Pubmed Central ID

  • 18830857

Electronic International Standard Serial Number (EISSN)

  • 1366-5804

International Standard Serial Number (ISSN)

  • 1354-750X

Digital Object Identifier (DOI)

  • 10.1080/13547500802445199

Language

  • eng