A blood-based screening tool for Alzheimer's disease that spans serum and plasma: findings from TARC and ADNI.

<h4>Context</h4>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.<h4>Objective</h4>To generate and cross-validate a blood-based screener for AD that yields acceptable acc...

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Autores principales:	Sid E O'Bryant, Guanghua Xiao, Robert Barber, Ryan Huebinger, Kirk Wilhelmsen, Melissa Edwards, Neill Graff-Radford, Rachelle Doody, Ramon Diaz-Arrastia, Texas Alzheimer's Research & Care Consortium, Alzheimer's Disease Neuroimaging Initiative
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/78929cbbf9f34eabb44c5fc8dbcf2cd4
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spelling	oai:doaj.org-article:78929cbbf9f34eabb44c5fc8dbcf2cd42021-11-18T07:32:52ZA blood-based screening tool for Alzheimer's disease that spans serum and plasma: findings from TARC and ADNI.1932-620310.1371/journal.pone.0028092https://doaj.org/article/78929cbbf9f34eabb44c5fc8dbcf2cd42011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22163278/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Context</h4>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.<h4>Objective</h4>To generate and cross-validate a blood-based screener for AD that yields acceptable accuracy across both serum and plasma.<h4>Design, setting, participants</h4>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.<h4>Major outcome measures</h4>Alzheimer's disease.<h4>Results</h4>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).<h4>Conclusions</h4>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.Sid E O'BryantGuanghua XiaoRobert BarberRyan HuebingerKirk WilhelmsenMelissa EdwardsNeill Graff-RadfordRachelle DoodyRamon Diaz-ArrastiaTexas Alzheimer's Research & Care ConsortiumAlzheimer's Disease Neuroimaging InitiativePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e28092 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sid E O'Bryant Guanghua Xiao Robert Barber Ryan Huebinger Kirk Wilhelmsen Melissa Edwards Neill Graff-Radford Rachelle Doody Ramon Diaz-Arrastia Texas Alzheimer's Research & Care Consortium Alzheimer's Disease Neuroimaging Initiative A blood-based screening tool for Alzheimer's disease that spans serum and plasma: findings from TARC and ADNI.
description	<h4>Context</h4>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.<h4>Objective</h4>To generate and cross-validate a blood-based screener for AD that yields acceptable accuracy across both serum and plasma.<h4>Design, setting, participants</h4>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.<h4>Major outcome measures</h4>Alzheimer's disease.<h4>Results</h4>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).<h4>Conclusions</h4>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.
format	article
author	Sid E O'Bryant Guanghua Xiao Robert Barber Ryan Huebinger Kirk Wilhelmsen Melissa Edwards Neill Graff-Radford Rachelle Doody Ramon Diaz-Arrastia Texas Alzheimer's Research & Care Consortium Alzheimer's Disease Neuroimaging Initiative
author_facet	Sid E O'Bryant Guanghua Xiao Robert Barber Ryan Huebinger Kirk Wilhelmsen Melissa Edwards Neill Graff-Radford Rachelle Doody Ramon Diaz-Arrastia Texas Alzheimer's Research & Care Consortium Alzheimer's Disease Neuroimaging Initiative
author_sort	Sid E O'Bryant
title	A blood-based screening tool for Alzheimer's disease that spans serum and plasma: findings from TARC and ADNI.
title_short	A blood-based screening tool for Alzheimer's disease that spans serum and plasma: findings from TARC and ADNI.
title_full	A blood-based screening tool for Alzheimer's disease that spans serum and plasma: findings from TARC and ADNI.
title_fullStr	A blood-based screening tool for Alzheimer's disease that spans serum and plasma: findings from TARC and ADNI.
title_full_unstemmed	A blood-based screening tool for Alzheimer's disease that spans serum and plasma: findings from TARC and ADNI.
title_sort	blood-based screening tool for alzheimer's disease that spans serum and plasma: findings from tarc and adni.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/78929cbbf9f34eabb44c5fc8dbcf2cd4
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A blood-based screening tool for Alzheimer's disease that spans serum and plasma: findings from TARC and ADNI.

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