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


CONCLUSIONS
These results suggest novel serum AD diagnostic biomarkers can be found using this approach.
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
Dipti Jigar
DJ
Shah
Department of Biology, Brigham Young University, Provo, UT, USA.
Frederick
F
Rohlfing
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
Swati
S
Anand
Division of Computational Biomedicine, Boston University School of Medicine, Boston University, Boston, MA, USA.
W Evan
WE
Johnson
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
MeiHwa Tanielle Bench
MT
Alvarez
Department of Biology, Brigham Young University, Provo, UT, USA.
Jesse
J
Cobell
Department of Biology, Brigham Young University, Provo, UT, USA.
Jackson
J
King
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
Sydney A
SA
Young
Department of Biology, Brigham Young University, Provo, UT, USA.
John S K
JS
Kauwe
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
Steven W
SW
Graves
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D012372:ROC Curve; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
D015415:Biomarkers
Alzheimer’s disease; diagnosis; lipidomics; mass spectrometry; proteomics; serum biomarkers