Concordance of CSF measures of Alzheimer's pathology with amyloid PET status in a preclinical cohort: A comparison of Lumipulse and established immunoassays

INTRODUCTION We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (A beta) and tau measured on the fully automated Lumipulse platform with pre-symptomatic Alzheimer's disease (AD) pathology on amyloid positron emission tomography (PET). METHODS In 72 individuals from the Insight 46 study, CSF A beta 40, A beta 42, total tau (t-tau), and phosphorylated tau at site 181 (p-tau181) were measured using Lumipulse, INNOTEST, and Meso Scale Discovery (MSD) assays and inter-platform Pearson correlations derived. Lumipulse A beta 42 measures were adjusted to incorporate standardization to certified reference materials. Logistic regressions and receiver operating characteristics analysis generated CSF cut-points optimizing concordance with F-18-florbetapir amyloid PET status (n = 63). RESULTS Measurements of CSF A beta, p-tau181, and their ratios correlated well across platforms (r 0.84 to 0.94, P < .0001); those of t-tau and t-tau/A beta 42 correlated moderately (r 0.57 to 0.79, P < .0001). The best concordance with amyloid PET (100% sensitivity and 94% specificity) was afforded by cut-points of 0.075 for Lumipulse A beta 42/A beta 40, 0.087 for MSD A beta 42/A beta 40 and 17.3 for Lumipulse A beta 42/p-tau181. DISCUSSION The Lumipulse platform provides comparable sensitivity and specificity to established CSF immunoassays in identifying pre-symptomatic AD pathology.

Automated summary

The study assessed the concordance of CSF amyloid beta and tau measured on the Lumipulse platform with pre-symptomatic AD pathology on amyloid PET. Results showed that Lumipulse platform provides comparable sensitivity and specificity to established CSF immunoassays in identifying pre-symptomatic AD pathology.