Cerebrospinal fluid proteomic biomarkers for Alzheimer's disease.
OBJECTIVE
To find a panel of proteins in antemortem cerebrospinal fluid (CSF) that could be used to differentiate between samples from Alzheimer's disease (AD) patients and samples from healthy and neurological control subjects.


METHODS
For a test cohort, antemortem CSF proteins from 34 AD and 34 non-AD patients were separated using two-dimensional gel electrophoresis. The resulting protein patterns were analyzed using the random forest multivariate statistical method. Protein spots of interest were identified using tandem time-of-flight mass spectrometry. A validation cohort consisting of CSF from 18 AD patients and 10 non-AD subjects was analyzed in a similar way.


RESULTS
Using the test cohort, a panel of 23 spots was identified that could be used to differentiate AD and non-AD gels with a sensitivity of 94%, a specificity of 94%, and a predicted classification error rate of only 5.9%. These proteins are related to the transport of beta-amyloid, the inflammatory response, proteolytic inhibition, and neuronal membrane proteins. The 23 spots separately classified the validation cohort with 90% sensitivity (probable AD subjects), 83% specificity, and a predicted classification error rate of 14% in a blinded analysis. The total observed sensitivity is 93%, the total observed specificity is 90%, and the predicted classification error rate is 8.3%.


CONCLUSIONS
A panel of possible CSF biomarkers for AD has been identified using proteomic methods.
Finehout
Erin J
EJ
School of Chemical and Biomolecular Engineering, Department of Nuerology and Neuroscience, Cornell University Medical College, Ithaca, NY 14853-5201, USA.
Franck
Zsofia
Z
Choe
Leila H
LH
Relkin
Norman
N
Lee
Kelvin H
KH
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D015331:Cohort Studies; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D040901:Proteomics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016037:Single-Blind Method; D053719:Tandem Mass Spectrometry
D015415:Biomarkers