AD and ADRD Differences in Luminex and Lumipulse ATN Categories

Abstract

AbstractBackgroundCerebrospinal fluid (CSF) biomarkers for amyloid (A), tau (T), and neurodegeneration (N) can be utilized to define pre‐mortem pathological status (ATN research framework). However, potential differences across methods present challenges when comparing studies. Our objective was to determine the ATN status in an AD/ADRD cohort using two different methods for measuring CSF AD‐related biomarkers; Fujirebio Lumipulse G1200 and the Luminex 200. The hypothesis was that the proportion of individuals in a given ATN category would differ between these two methods.MethodParticipants were recruited from the Cleveland Alzheimer’s Disease Research Center (CADRC), and Cleveland Clinic Lou Ruvo Center for Brain Health (CBH) and included cognitively normal (CN), mild cognitive impairment (MCI), AD, dementia with Lewy Bodies (DLB), and PD patient groups. Aβ42/40 (A), p‐Tau181 (T) and t‐Tau (N) were quantitated using both Lumipulse and Luminex systems. Receiver Operating Characteristic (ROC) curve was utilized to identify optimal cutpoints for the three biomarkers (A, T, and N) based on the CN and AD cohorts. Youden index was calculated to identify the strength of these biomarkers.ResultCorrelation analyses between the two platforms, indicated that there was a significant correlation for Aβ42/40 (A), p‐Tau181 (T) and t‐Tau (N) among most patient groups, especially for Aβ42/40. The cut‐points were 0.0562 (A), 65 pg/mL (T) and 345 pg/mL (N) for Lumipulse, and 0.1600 (A), 106.77 pg/mL (T) and 399.41 pg/mL (N) for Luminex. Out of the overall cohort of 283 individuals, over half had identical ATN status for both Lumipulse and Luminex.ConclusionThere was a strong correlation for CSF AD‐related biomarkers between the two platforms. However, there was a lack of complete ATN category overlap between platforms suggesting that across study comparisons using ATN categories derived from different platforms (e.g. Luminex and Lumipulse) should be approached with caution. In light of different techniques that are available, it is important to understand the difference between them to inform standardization and data harmonization efforts. A definite and effective method to quantitate AD related biomarkers holds the promise of better differential diagnosis in individuals with AD and ADRD.