title: A blood-based screening tool for Alzheimer's disease that spans serum and plasma: findings from TARC and ADNI.
abstract: BACKGROUND
  There is no rapid and cost effective tool that can be implemented as a front-line screening tool for Alzheimer's disease (AD) at the population level.
  
  
  OBJECTIVE
  To generate and cross-validate a blood-based screener for AD that yields acceptable accuracy across both serum and plasma.
  
  
  METHODS
  Analysis of serum biomarker proteins were conducted on 197 Alzheimer's disease (AD) participants and 199 control participants from the Texas Alzheimer's Research Consortium (TARC) with further analysis conducted on plasma proteins from 112 AD and 52 control participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The full algorithm was derived from a biomarker risk score, clinical lab (glucose, triglycerides, total cholesterol, homocysteine), and demographic (age, gender, education, APOE*E4 status) data.
  
  
  METHODS
  Alzheimer's disease.
  
  
  RESULTS
  11 proteins met our criteria and were utilized for the biomarker risk score. The random forest (RF) biomarker risk score from the TARC serum samples (training set) yielded adequate accuracy in the ADNI plasma sample (training set) (AUC = 0.70, sensitivity (SN) = 0.54 and specificity (SP) = 0.78), which was below that obtained from ADNI cerebral spinal fluid (CSF) analyses (t-tau/Aβ ratio AUC = 0.92). However, the full algorithm yielded excellent accuracy (AUC = 0.88, SN = 0.75, and SP = 0.91). The likelihood ratio of having AD based on a positive test finding (LR+) = 7.03 (SE = 1.17; 95% CI = 4.49-14.47), the likelihood ratio of not having AD based on the algorithm (LR-) = 3.55 (SE = 1.15; 2.22-5.71), and the odds ratio of AD were calculated in the ADNI cohort (OR) = 28.70 (1.55; 95% CI = 11.86-69.47).
  
  
  CONCLUSIONS
  It is possible to create a blood-based screening algorithm that works across both serum and plasma that provides a comparable screening accuracy to that obtained from CSF analyses.
authors.affiliation: Department of Neurology, F. Marie Hall Institute for Rural and Community Health, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America. Sid.Obryant@ttuhsc.edu
authors.forename: Sid E
authors.initials: SE
authors.lastname: O'Bryant
authors.forename: Guanghua
authors.initials: G
authors.lastname: Xiao
authors.forename: Robert
authors.initials: R
authors.lastname: Barber
authors.forename: Ryan
authors.initials: R
authors.lastname: Huebinger
authors.forename: Kirk
authors.initials: K
authors.lastname: Wilhelmsen
authors.forename: Melissa
authors.initials: M
authors.lastname: Edwards
authors.forename: Neill
authors.initials: N
authors.lastname: Graff-Radford
authors.forename: Rachelle
authors.initials: R
authors.lastname: Doody
authors.forename: Ramon
authors.initials: R
authors.lastname: Diaz-Arrastia
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis*; D053327:Apolipoprotein E4 / Q000235:genetics; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D002555:Cerebrospinal Fluid / Q000378:metabolism; D015331:Cohort Studies; D019295:Computational Biology / Q000379:methods; D005260:Female; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D010949:Plasma / Q000378:metabolism*; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D044967:Serum / Q000378:metabolism*; D013781:Texas
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers