A serum protein-based algorithm for the detection of Alzheimer disease.
OBJECTIVE
To develop an algorithm that separates patients with Alzheimer disease (AD) from controls.


METHODS
Longitudinal case-control study.


METHODS
The Texas Alzheimer's Research Consortium project. Patients  We analyzed serum protein-based multiplex biomarker data from 197 patients diagnosed with AD and 203 controls. Main Outcome Measure  The total sample was randomized equally into training and test sets and random forest methods were applied to the training set to create a biomarker risk score.


RESULTS
The biomarker risk score had a sensitivity and specificity of 0.80 and 0.91, respectively, and an area under the curve of 0.91 in detecting AD. When age, sex, education, and APOE status were added to the algorithm, the sensitivity, specificity, and area under the curve were 0.94, 0.84, and 0.95, respectively.


CONCLUSIONS
These initial data suggest that serum protein-based biomarkers can be combined with clinical information to accurately classify AD. A disproportionate number of inflammatory and vascular markers were weighted most heavily in the analyses. Additionally, these markers consistently distinguished cases from controls in significant analysis of microarray, logistic regression, and Wilcoxon analyses, suggesting the existence of an inflammatory-related endophenotype of AD that may provide targeted therapeutic opportunities for this subset of patients.
O'Bryant
Sid E
SE
Texas Tech University Health Science Center, Department of Neurology, Lubbock, TX 79430, USA. sid.obryant@ttuhsc.edu
Xiao
Guanghua
G
Barber
Robert
R
Reisch
Joan
J
Doody
Rachelle
R
Fairchild
Thomas
T
Adams
Perrie
P
Waring
Steven
S
Diaz-Arrastia
Ramon
R
D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis*; D001057:Apolipoproteins E / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis*; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity
D001057:Apolipoproteins E; D015415:Biomarkers; D001798:Blood Proteins