Discovery and Subsequent Confirmation of Novel Serum Biomarkers Diagnosing Alzheimer’s Disease

Autor: MeiHwa Tanielle Bench Alvarez, John S. K. Kauwe, Frederick Rohlfing, Jesse Cobell, Jackson King, Sydney A Young, Swati Anand, Dipti Jigar Shah, W. Evan Johnson, Steven W. Graves
Rok vydání: 2015
Předmět:
Zdroj: Journal of Alzheimer's Disease. 49:317-327
ISSN: 1875-8908
1387-2877
Popis: Background: Alzheimer’s disease (AD) remains challenging to diagnose, especially early disease. Having serum AD biomarkers would be of significant interest both in the clinical setting and in drug development efforts. Objective: We applied a novel serum proteomic approach to interrogate the low-molecular weight proteome for serum AD biomarkers. Methods: A discovery study used sera from 58 any-stage AD cases and 55 matched controls analyzed by capillary liquid chromatography-electrospray ionization-tandem mass spectrometry. Candidate biomarkers were statistically modeled and promising biomarkers were retested in a second, blinded confirmatory study (AD cases = 68, controls = 57). Biomarkers that replicated in the second study were modeled for the diagnosis of any-stage and very early stage AD. Further, they were chemically identified by tandem MS. Results: The initial discovery study found 59 novel potential AD biomarkers. Thirteen recurred in more than one multi-marker panel. In a second, blinded, confirmatory study, these same biomarkers were retested in separate specimens. In that study, four markers validated comparing controls to patients with any-stage AD and also with very early AD. The four biomarkers with replicable ability to diagnose AD were then chemically identified. Conclusion: These results suggest novel serum AD diagnostic biomarkers can be found using this approach.
Databáze: OpenAIRE