Austin Health

Title
Concordance Between Cerebrospinal Fluid Biomarkers with Alzheimer's Disease Pathology Between Three Independent Assay Platforms.
Publication Date
2018
Author(s)
Doecke, James D
Rembach, Alan
Villemagne, Victor L
Varghese, Shiji
Rainey-Smith, Stephanie R
Sarros, Shannon
Evered, Lisbeth A
Fowler, Christopher J
Pertile, Kelly K
Rumble, Rebecca L
Trounson, Brett
Taddei, Kevin
Laws, Simon M
Macaulay, S Lance
Bush, Ashley I
Ellis, Kathryn A
Martins, Ralph
Ames, David
Silbert, Brendan
Vanderstichele, Hugo
Masters, Colin L
Darby, David G
Li, Qiao-Xin
Collins, Steven
Subject
Amyloid
PET
biomarker
cerebrospinal fluid
concordance
Type of document
Journal Article
DOI
10.3233/JAD-170128
Abstract
To enhance the accuracy of clinical diagnosis for Alzheimer's disease (AD), pre-mortem biomarkers have become increasingly important for diagnosis and for participant recruitment in disease-specific treatment trials. Cerebrospinal fluid (CSF) biomarkers provide a low-cost alternative to positron emission tomography (PET) imaging for in vivo quantification of different AD pathological hallmarks in the brains of affected subjects; however, consensus around the best platform, most informative biomarker and correlations across different methodologies are controversial. Assessing levels of Aβ-amyloid and tau species determined using three different versions of immunoassays, the current study explored the ability of CSF biomarkers to predict PET Aβ-amyloid (32 Aβ-amyloid-and 45 Aβ-amyloid+), as well as concordance between CSF biomarker levels and PET Aβ-amyloid imaging. Prediction and concordance analyses were performed using a sub-cohort of 77 individuals (48 healthy controls, 15 with mild cognitive impairment, and 14 with AD) from the Australian Imaging Biomarker and Lifestyle study of aging. Across all three platforms, the T-tau/Aβ42 ratio biomarker had modestly higher correlation with SUVR/BeCKeT (ρ= 0.69-0.8) as compared with Aβ42 alone (ρ= 0.66-0.75). Differences in CSF biomarker levels between the PET Aβ-amyloid-and Aβ-amyloid+ groups were strongest for the Aβ42/Aβ40 and T-tau/Aβ42 ratios (p < 0.0001); however, comparison of predictive models for PET Aβ-amyloid showed no difference between Aβ42 alone and the T-tau/Aβ42 ratio. This study confirms strong concordance between CSF biomarkers and PET Aβ-amyloid status is independent of immunoassay platform, supporting their utility as biomarkers in clinical practice for the diagnosis of AD and for participant enrichment in clinical trials.
Link
Citation
Journal of Alzheimer's disease : JAD 2018; 61(1): 169-183
Jornal Title
Journal of Alzheimer's disease : JAD

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