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.

Agreement of amyloid PET and CSF biomarkers for Alzheimer's disease on Lumipulse.

OBJECTIVE: To determine the cutoffs that optimized the agreement between 18 F-Florbetapir positron emission tomography (PET) and Aß1-42, Aß1-40, tTau, pTau and their ratios measured in cerebrospinal fluid (CSF) on the LUMIPULSE G600II instrument, we quantified the levels of these four biomarkers in 94 CSF samples from participants of the Sant Pau Initiative on Neurodegeneration (SPIN cohort) using the Lumipulse G System with available 18 F-Florbetapir imaging. METHODS: Participants had mild cognitive impairment (n = 35), AD dementia (n = 12), other dementias or neurodegenerative diseases (n = 41), or were cognitively normal controls (n = 6). Levels of Aß1-42 were standardized to certified reference material. Amyloid scans were assessed visually and through automated quantification. We determined the cutoffs of CSF biomarkers that optimized their agreement with 18 F-Florbetapir PET and evaluated concordance between markers of the amyloid category. RESULTS: Aß1-42, tTau and pTau (but not Aß1-40) and the ratios with Aß1-42 had good diagnostic agreement with 18 F-Florbetapir PET. As a marker of amyloid pathology, the Aß1-42/Aß1-40 ratio had higher agreement and better correlation with amyloid PET than Aß1-42 alone. INTERPRETATION: CSF biomarkers measured with the Lumipulse G System show good agreement with amyloid imaging in a clinical setting with heterogeneous presentations of neurological disorders. Combination of Aß1-42 with Aß1-40 increases the agreement between markers of amyloid pathology.

Evaluation of Versant hepatitis C virus genotype assay (LiPA) 2.0.

Hepatitis C virus (HCV) genotyping is a tool used to optimize antiviral treatment regimens. The newly developed Versant HCV genotype assay (LiPA) 2.0 uses sequence information from both the 5' untranslated region and the core region, allowing distinction between HCV genotype 1 and subtypes c to l of genotype 6 and between subtypes a and b of genotype 1. HCV-positive samples were genotyped manually using the Versant HCV genotype assay (LiPA) 2.0 system according to the manufacturer's instructions. For the comparison study, Versant HCV genotype assay (LiPA) 1.0 was used. In this study, 99.7% of the samples could be amplified, the genotype of 96.0% of samples could be determined, and the agreement with the reference method was 99.4% when a genotype was determined. The reproducibility study showed no significant differences in performance across sites (P = 0.43) or across lots (P = 0.88). In the comparison study, 13 samples that were uninterpretable or incorrectly genotyped with Versant HCV genotype assay (LiPA) 1.0 were correctly genotyped by Versant HCV genotype assay (LiPA) 2.0. Versant HCV genotype assay (LiPA) 2.0 is a sensitive, accurate, and reliable assay for HCV genotyping. The inclusion of the core region probes in Versant HCV genotype assay (LiPA) 2.0 results in a genotyping success rate higher than that of the current Versant HCV genotype assay (LiPA) 1.0.