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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.

Original publication

DOI

10.1080/13547500802445199

Type

Journal article

Journal

Biomarkers

Publication Date

09/2008

Volume

13

Pages

618 - 636

Keywords

Aged, Alzheimer Disease, Apolipoproteins E, Biomarkers, Cognition, Complement C1 Inactivator Proteins, Complement C1 Inhibitor Protein, Complement Factor H, Dose-Response Relationship, Drug, Double-Blind Method, Europe, Female, Humans, Male, Middle Aged, New Zealand, Nootropic Agents, Proteomics, Reproducibility of Results, Rosiglitazone, Severity of Illness Index, Thiazolidinediones, Time Factors, Treatment Outcome, alpha-Macroglobulins