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Blood-based protein biomarkers for diagnosis of Alzheimer disease.

ABSTRACT: 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, ?(2) microglobulin, vascular cell adhesion molecule 1, carcinoembryonic antigen, matrix metalloprotein 2, CD40, macrophage inflammatory protein 1?, 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.

SUBMITTER: Doecke JD

PROVIDER: S-EPMC6287606 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Blood-based protein biomarkers for diagnosis of Alzheimer disease.

Doecke James D JD Laws Simon M SM Faux Noel G NG Wilson William W Burnham Samantha C SC Lam Chiou-Peng CP Mondal Alinda A Bedo Justin J Bush Ashley I AI Brown Belinda B De Ruyck Karl K Ellis Kathryn A KA Fowler Christopher C Gupta Veer B VB Head Richard R Macaulay S Lance SL Pertile Kelly K Rowe Christopher C CC Rembach Alan A Rodrigues Mark M Rumble Rebecca R Szoeke Cassandra C Taddei Kevin K Taddei Tania T Trounson Brett B Ames David D Masters Colin L CL Martins Ralph N RN

Archives of neurology 20121001 10

<h4>Objective</h4>To identify plasma biomarkers for the diagnosis of Alzheimer disease (AD).<h4>Design</h4>Baseline plasma screening of 151 multiplexed analytes combined with targeted biomarker and clinical pathology data.<h4>Setting</h4>General community-based, prospective, longitudinal study of aging.<h4>Participants</h4>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 bio ...[more]

PMID: 22801742

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Project description:Background and objectiveBlood biomarkers for Alzheimer disease (AD) have consistently proven to be associated with CSF or PET biomarkers and effectively discriminate AD from other neurodegenerative diseases. Our aim was to test their utility in clinical practice, from a multicentric unselected prospective cohort where patients presented with a large spectrum of cognitive deficits or complaints.MethodsThe MEMENTO cohort enrolled 2,323 outpatients with subjective cognitive complaint (SCC) or mild cognitive impairment (MCI) consulting in 26 French memory clinics. Participants had neuropsychological assessments, MRI, and blood sampling at baseline. CSF sampling and amyloid PET were optional. Baseline blood Aβ42/40 ratio, total tau, p181-tau, and neurofilament light chain (NfL) were measured using a Simoa HD-X analyzer. An expert committee validated incident dementia cases during a 5-year follow-up period.ResultsOverall, 2,277 individuals had at least 1 baseline blood biomarker available (n = 357 for CSF subsample, n = 649 for PET subsample), among whom 257 were diagnosed with clinical AD/mixed dementia during follow-up. All blood biomarkers but total tau were mildly correlated with their equivalence in the CSF (r = 0.33 to 0.46, p < 0.0001) and were associated with amyloid-PET status (p < 0.0001). Blood p181-tau was the best blood biomarker to identify amyloid-PET positivity (area under the curve = 0.74 [95% CI = 0.69; 0.79]). Higher blood and CSF p181-tau and NfL concentrations were associated with accelerated time to AD dementia onset with similar incidence rates, whereas blood Aβ42/40 was less efficient than CSF Aβ42/40. Blood p181-tau alone was the best blood predictor of 5-year AD/mixed dementia risk (c-index = 0.73 [95% CI = 0.69; 0.77]); its accuracy was higher in patients with clinical dementia rating (CDR) = 0 (c-index = 0.83 [95% CI = 0.69; 0.97]) than in patients with CDR = 0.5 (c-index = 0.70 [95% CI = 0.66; 0.74]). A "clinical" reference model (combining demographics and neuropsychological assessment) predicted AD/mixed dementia risk with a c-index = 0.88 [95% CI = 0.86-0.91] and performance increased to 0.90 [95% CI = 0.88; 0.92] when adding blood p181-tau + Aβ42/40. A "research" reference model (clinical model + apolipoprotein E genotype and AD signature on MRI) had a c-index = 0.91 [95% CI = 0.89-0.93] increasing to 0.92 [95% CI = 0.90; 0.93] when adding blood p181-tau + Aβ42/40. Chronic kidney disease and vascular comorbidities did not affect predictive performances.DiscussionIn a clinic-based cohort of patients with SCC or MCI, blood biomarkers may be good hallmarks of underlying pathology but add little to 5-year dementia risk prediction models including traditional predictors.

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Blood-based protein biomarkers for diagnosis of Alzheimer disease.

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Blood-based protein biomarkers for diagnosis of Alzheimer disease.

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