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

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 A beta-amyloidand tau species determined using three different versions of immunoassays, the current study explored the ability of CSF biomarkers to predict PET A beta-amyloid (32 A beta-amyloid-and 45 A beta-amyloid+), as well as concordance between CSF biomarker levels and PET A beta-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/A beta(42) ratio biomarker had modestly higher correlation with SUVR/BeCKeT (rho = 0.69-0.8) as compared with A beta(42) alone (rho = 0.66-0.75). Differences in CSF biomarker levels between the PET A beta-amyloid-and A beta-amyloid+groups were strongest for the A beta(42)/A beta(40) and T-tau/A beta(42) ratios (p < 0.0001); however, comparison of predictive models for PET A beta-amyloid showed no difference between A beta(42) alone and the T-tau/A beta(42) ratio. Conclusion: This study confirms strong concordance between CSF biomarkers and PET A beta-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.