A blood-based screening tool for Alzheimer's disease that spans serum and plasma

Findings from TARC and ADNI

Sid E. O'Bryant, Guanghua Xiao, Robert Barber, Ryan Huebinger, Kirk Wilhelmsen, Melissa Edwards, Neill Graff-Radford, Rachelle Doody, Ramon Diaz-Arrastia

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Context: 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. Design, Setting, Participants: 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. Major Outcome Measures: 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.

Original languageEnglish (US)
Article numbere28092
JournalPLoS One
Volume6
Issue number12
DOIs
StatePublished - Dec 7 2011

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Neuroimaging
Alzheimer disease
blood serum
Alzheimer Disease
Screening
Blood
screening
Plasmas
blood
Serum
Research
Biomarkers
biomarkers
Area Under Curve
Blood Proteins
Sensitivity and Specificity
Fluids
homocysteine
Homocysteine
odds ratio

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

A blood-based screening tool for Alzheimer's disease that spans serum and plasma : Findings from TARC and ADNI. / O'Bryant, Sid E.; Xiao, Guanghua; Barber, Robert; Huebinger, Ryan; Wilhelmsen, Kirk; Edwards, Melissa; Graff-Radford, Neill; Doody, Rachelle; Diaz-Arrastia, Ramon.

In: PLoS One, Vol. 6, No. 12, e28092, 07.12.2011.

Research output: Contribution to journalArticle

O'Bryant, SE, Xiao, G, Barber, R, Huebinger, R, Wilhelmsen, K, Edwards, M, Graff-Radford, N, Doody, R & Diaz-Arrastia, R 2011, 'A blood-based screening tool for Alzheimer's disease that spans serum and plasma: Findings from TARC and ADNI', PLoS One, vol. 6, no. 12, e28092. https://doi.org/10.1371/journal.pone.0028092
O'Bryant, Sid E. ; Xiao, Guanghua ; Barber, Robert ; Huebinger, Ryan ; Wilhelmsen, Kirk ; Edwards, Melissa ; Graff-Radford, Neill ; Doody, Rachelle ; Diaz-Arrastia, Ramon. / A blood-based screening tool for Alzheimer's disease that spans serum and plasma : Findings from TARC and ADNI. In: PLoS One. 2011 ; Vol. 6, No. 12.
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abstract = "Context: 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. Design, Setting, Participants: 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. Major Outcome Measures: 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.",
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