Affiliations: [a] Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA | [b] Department of Biology, Brigham Young University, Provo, UT, USA | [c] Division of Computational Biomedicine, Boston University School of Medicine, Boston University, Boston, MA, USA
Correspondence:
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Correspondence to: Dr. Steven W. Graves, Department of Chemistry and Biochemistry, BNSN C212, Brigham Young University, Provo, 84602 UT, USA. Tel.: +1 801 422 2148; Fax: +1 801 422 0153; E-mail: [email protected]
Abstract: 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.
Keywords: Alzheimer’s disease, diagnosis, lipidomics, mass spectrometry, proteomics, serum biomarkers
