• James D Doecke, Alan Rembach, Victor L Villemagne, Shiji Varghese, Stephanie Rainey-Smith, Shannon Sarros, Lisbeth A Evered, Christopher J Fowler, Kelly K Pertile, Rebecca L Rumble, Brett Trounson, Kevin Taddei, Simon M Laws, S Lance Macaulay, Ashley I Bush, Kathryn A Ellis, Ralph Martins, David Ames, Brendan Silbert, Hugo Vanderstichele, Colin L Masters, David G Darby, Qiao-Xin Li, Steven Collins, and AIBL Research Group.
• CSIRO Health and Biosecurity/Australian e-Health Research Centre, Brisbane, QLD, Australia.
• J. Alzheimers Dis. 2018 Jan 1; 61 (1): 169-183.

BackgroundTo 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.ObjectiveAssessing 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.MethodsPrediction 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.ResultsAcross 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.ConclusionThis 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.

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