Concordance Between Cerebrospinal Fluid Biomarkers with Alzheimer’s Disease Pathology Between Three Independent Assay Platforms

Article type: Research Article

Authors: Doecke, James D.^{a; b} | Rembach, Alan^{c; †} | Villemagne, Victor L.^{c; d} | Varghese, Shiji^{c; k} | Rainey-Smith, Stephanie^e | Sarros, Shannon^{c; k} | Evered, Lisbeth A.^f | Fowler, Christopher J.^c | Pertile, Kelly K.^c | Rumble, Rebecca L.^c | Trounson, Brett^c | Taddei, Kevin^e | Laws, Simon M.^e | Macaulay, S. Lance^a | Bush, Ashley I.^c | Ellis, Kathryn A.^g | Martins, Ralph^e | Ames, David^g | Silbert, Brendan^f | Vanderstichele, Hugo^h | Masters, Colin L.^{c; k} | Darby, David G.^c | Li, Qiao-Xin^{c; k} | Collins, Steven^{c; i; k; *} | the AIBL Research Group^j

Affiliations: [a] CSIRO Health and Biosecurity/Australian e-Health Research Centre, Brisbane, QLD, Australia | [b] Cooperative Research Centre for Mental Health, Parkville, VIC, Australia | [c] The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia | [d] Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia | [e] Sir James McCusker Alzheimer’s Disease Research Unit (Hollywood Private Hospital), Perth, WA, Australia | [f] Department of Anaesthesia and Perioperative Pain Medicine, Centre for Anaesthesia and Cognitive Function, St Vincent’s Hospital, Melbourne, Australia | [g] Academic Unit for Psychiatry of Old Age, The University of Melbourne, Melbourne, Australia | [h] ADx NeuroSciences, Gent, Belgium | [i] Department of Medicine (RMH), The University of Melbourne, Parkville, Australia | [j] http://aibl.csiro.au | [k] National Dementia Diagnostics Laboratory, The University of Melbourne, VIC, Australia

Correspondence: [*] Correspondence to: Steven Collins, Department of Medicine (RHM) and The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3052, Australia. Tel.: +61 3 9035 3000; E-mail: s.collins@unimelb.edu.au.

Note: [†] Unexpectedly deceased 20 November 2014.

Abstract: Background: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. Objective: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. Methods: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. Results: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. Conclusion: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.

Keywords: Amyloid, biomarker, cerebrospinal fluid, concordance, PET

DOI: 10.3233/JAD-170128

Journal: Journal of Alzheimer's Disease, vol. 61, no. 1, pp. 169-183, 2018