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

J Alzheimers Dis. 2016;49(2):317-27. doi: 10.3233/JAD-150498.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Alzheimer Disease / diagnosis*
  • Biomarkers / blood*
  • Case-Control Studies
  • Chromatography, Liquid
  • Female
  • Humans
  • Male
  • Psychiatric Status Rating Scales
  • ROC Curve
  • Reproducibility of Results
  • Tandem Mass Spectrometry


  • Biomarkers