Concordance of Lumipulse cerebrospinal fluid t-tau/Aß42 ratio with amyloid PET status.

INTRODUCTION: Cerebrospinal fluid (CSF) biomarkers can identify individuals with Alzheimer's disease (AD) pathology (eg, amyloid plaques, neurofibrillary tangles), but defined analyte cut-points using high-throughput automated assays are necessary for general clinical use. METHODS: CSF amyloid ß42 peptide (Aß42), t-tau, and t-tau/Aß42 were quantified by the Lumipulse platform in two test cohorts (A/B: Eisai BAN2401-201/MISSION AD E2609-301/302, n = 138; C: Knight Alzheimer's Disease Research Center (ADRC), n = 198), and receiver operating characteristic (ROC) curve analyses defined cut-points corresponding best to amyloid determinations using positron emission tomography (PET) imaging. The best-performing cut-point was then validated as a predictor of amyloid status in an independent cohort (D: MISSION AD E2609-301/302, n = 240). RESULTS: Virtually identical t-tau/Aß42 cut-points (∼0.54) performed best in both test cohorts and with similar accuracy (areas under ROC curve [AUCs] [A/B: 0.95; C: 0.94]). The cut-point yielded an overall percent agreement with amyloid PET of 85.0% in validation cohort D. DISCUSSION: Lumipulse CSF biomarker measures with validated cut-points have clinical utility in identifying AD pathology.

Effect of Patient-Specific Preanalytic Variables on CSF Aß1-42 Concentrations Measured on an Automated Chemiluminescent Platform.

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers are increasingly used to confirm the accuracy of a clinical diagnosis of mild cognitive impairment or dementia due to Alzheimer disease (AD). Recent evidence suggests that fully automated assays reduce the impact of some preanalytical factors on the variability of these measures. This study evaluated the effect of several preanalytical variables common in clinical settings on the variability of CSF ß-amyloid 1-42 (Aß1-42) concentrations. METHODS: Aß1-42 concentrations were measured using the LUMIPULSE G1200 from both freshly collected and frozen CSF samples. Preanalytic variables examined were: (1) patient fasting prior to CSF collection, (2) blood contamination of specimens, and (3) aliquoting specimens sequentially over the course of collection (i.e., CSF gradients). RESULTS: Patient fasting did not significantly affect CSF Aß1-42 levels. While assessing gradient effects, Aß1-42 concentrations remained stable within the first 5 1-mL aliquots. However, there is evidence of a gradient effect toward higher concentrations over successive aliquots. Aß1-42 levels were stable when fresh CSF samples were spiked with up to 2.5% of blood. However, in frozen CSF samples, even 0.25% blood contamination significantly decreased Aß1-42 concentrations. CONCLUSIONS: The preanalytical variables examined here do not have significant effects on Aß1-42 concentrations if fresh samples are processed within 2 h. However, a gradient effect can be observed on Aß1-42 concentrations after the first 5 mL of collection and blood contamination has a significant impact on Aß1-42 concentrations once specimens have been frozen.