TY - JOUR
T1 - Blood-based protein biomarkers for diagnosis of Alzheimer disease
AU - Doecke, James D.
AU - Laws, Simon M.
AU - Faux, Noel G.
AU - Wilson, William
AU - Burnham, Samantha C.
AU - Lam, Chiou Peng
AU - Mondal, Alinda
AU - Bedo, Justin
AU - Bush, Ashley I.
AU - Brown, Belinda
AU - De Ruyck, Karl
AU - Ellis, Kathryn A.
AU - Fowler, Christopher
AU - Gupta, Veer B.
AU - Head, Richard
AU - Macaulay, S. Lance
AU - Pertile, Kelly
AU - Rowe, Christopher C.
AU - Rembach, Alan
AU - Rodrigues, Mark
AU - Rumble, Rebecca
AU - Szoeke, Cassandra
AU - Taddei, Kevin
AU - Taddei, Tania
AU - Trounson, Brett
AU - Ames, David
AU - Masters, Colin L.
AU - Martins, Ralph N.
AU - the Australian Imaging Biomarkers and Lifestyle (AIBL) Research Group
PY - 2012/10
Y1 - 2012/10
N2 - Objective: To identify plasma biomarkers for the diagnosis of Alzheimer disease (AD). Design: Baseline plasma screening of 151 multiplexed analytes combined with targeted biomarker and clinical pathology data. Setting: General community-based, prospective, longitudinal study of aging. Participants: A total of 754 healthy individuals serving as controls and 207 participants with AD from the Australian Imaging Biomarker and Lifestyle study (AIBL) cohort with identified biomarkers that were validated in 58 healthy controls and 112 individuals with AD from the Alzheimer Disease Neuroimaging Initiative (ADNI) cohort. Results: A biomarker panel was identified that included markers significantly increased (cortisol, pancreatic polypeptide, insulinlike growth factor binding protein 2, β2 microglobulin, vascular cell adhesion molecule 1, carcinoembryonic antigen, matrix metalloprotein 2, CD40, macrophage inflammatory protein 1α, superoxide dismutase, and homocysteine) and decreased (apolipoprotein E, epidermal growth factor receptor, hemoglobin, calcium, zinc, interleukin 17, and albumin) in AD. Cross-validated accuracy measures from the AIBL cohort reached a mean (SD) of 85% (3.0%) for sensitivity and specificity and 93% (3.0) for the area under the receiver operating characteristic curve . A second validation using the ADNI cohort attained accuracy measures of 80% (3.0%) for sensitivity and specificity and 85% (3.0) for area under the receiver operating characteristic curve. Conclusions: This study identified a panel of plasma biomarkers that distinguish individuals with AD from cognitively healthy control subjects with high sensitivity and specificity. Cross-validation within the AIBL cohort and further validation within the ADNI cohort provides strong evidence that the identified biomarkers are important for AD diagnosis.
AB - Objective: To identify plasma biomarkers for the diagnosis of Alzheimer disease (AD). Design: Baseline plasma screening of 151 multiplexed analytes combined with targeted biomarker and clinical pathology data. Setting: General community-based, prospective, longitudinal study of aging. Participants: A total of 754 healthy individuals serving as controls and 207 participants with AD from the Australian Imaging Biomarker and Lifestyle study (AIBL) cohort with identified biomarkers that were validated in 58 healthy controls and 112 individuals with AD from the Alzheimer Disease Neuroimaging Initiative (ADNI) cohort. Results: A biomarker panel was identified that included markers significantly increased (cortisol, pancreatic polypeptide, insulinlike growth factor binding protein 2, β2 microglobulin, vascular cell adhesion molecule 1, carcinoembryonic antigen, matrix metalloprotein 2, CD40, macrophage inflammatory protein 1α, superoxide dismutase, and homocysteine) and decreased (apolipoprotein E, epidermal growth factor receptor, hemoglobin, calcium, zinc, interleukin 17, and albumin) in AD. Cross-validated accuracy measures from the AIBL cohort reached a mean (SD) of 85% (3.0%) for sensitivity and specificity and 93% (3.0) for the area under the receiver operating characteristic curve . A second validation using the ADNI cohort attained accuracy measures of 80% (3.0%) for sensitivity and specificity and 85% (3.0) for area under the receiver operating characteristic curve. Conclusions: This study identified a panel of plasma biomarkers that distinguish individuals with AD from cognitively healthy control subjects with high sensitivity and specificity. Cross-validation within the AIBL cohort and further validation within the ADNI cohort provides strong evidence that the identified biomarkers are important for AD diagnosis.
UR - http://www.scopus.com/inward/record.url?scp=84867339786&partnerID=8YFLogxK
U2 - 10.1001/archneurol.2012.1282
DO - 10.1001/archneurol.2012.1282
M3 - Article
C2 - 22801742
AN - SCOPUS:84867339786
SN - 0003-9942
VL - 69
SP - 1318
EP - 1325
JO - Archives of Neurology
JF - Archives of Neurology
IS - 10
ER -