ABSTRACT
INTRODUCTION: The prognostic role of plasma neurofilament light chain (NfL), phospho-tau, beta-amyloid, and GFAP is still debated in Parkinson's disease (PD). METHODS: Plasma p-tau181, p-tau231, Aß1-40, Aß1-42, GFAP, and NfL were measured by SIMOA in 136 PD with 2.9 + 1.7 years of follow-up and 76 controls. Differences in plasma levels between controls and PD and their correlation with clinical severity and progression rates were evaluated using linear regression analyses. RESULTS: Patients exhibited similar distribution of plasma biomarkers but higher P-tau181, P-tau231 and lower Aß1-42 compared with controls. NfL and GFAP correlated with baseline motor and non-motor severity measures. At follow-up, NfL emerged as the best predictor of progression with marginal effect of GFAP and p-tau181 adjusting for age, sex, disease duration, and baseline motor severity. CONCLUSION: The present findings confirmed plasma NfL as best predictor of progression in PD, with a marginal role of p-tau181 and GFAP.
ABSTRACT
Aim of the project was to evaluate the technical and clinical validity of plasma Lumipulse p-tau, Aß42 and Aß40 species and their correlation with CSF core Alzheimer's Disease (AD) markers; a method comparison with SIMOA was also performed. One-hundred-thirthy-three participants, namely 55 A+T+N+ AD, 28 Neurodegenerative disorders (NDD) and 50 controls were enrolled for the study. Lumipulse technical validity showed high stability for p-tau181, Aß42, and Aß40, with higher stability of p-tau to repeated freezing thaw cycles. p-tau181 levels detected by both techniques were higher in AD compared to both NDD/controls and exhibited a similar correlation with CSF p-tau levels, whereas Aß42 levels were slightly lower in AD with both methods. In the comparison between SIMOA and Lumipulse plasma markers, both techniques exhibited similar diagnostic accuracy for AD for p-tau181 (0.87; 95â¯%CI 0.81-0.94, vs 0.85; 95â¯%CI 0.78-0.93), whereas the best performance was reached by p-tau181/ Aß42 Lumipulse ratio (ROC AUC 0.915, 95â¯%CI 0.86-0.97). The study thus confirmed the construct validity of both Lumipulse and SIMOA techniques for the identification of CSF AD pattern in clinical settings.
Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Biomarkers , tau Proteins , Alzheimer Disease/blood , Alzheimer Disease/diagnosis , Humans , tau Proteins/blood , tau Proteins/cerebrospinal fluid , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Amyloid beta-Peptides/blood , Amyloid beta-Peptides/cerebrospinal fluid , Female , Male , Aged , Middle Aged , Peptide Fragments/blood , Peptide Fragments/cerebrospinal fluid , Aged, 80 and overABSTRACT
Background: Plasma phosphorylated-tau217 (p-tau217) has been shown to be one of the most accurate diagnostic markers for Alzheimer's disease (AD). No studies have compared the clinical performance of p-tau217 as assessed by the fully automated Lumipulse and SIMOA ALZpath p-tau217. Aim: To evaluate the diagnostic accuracy of Lumipulse and SIMOA plasma p-tau217 assays for AD. Methods: The study included 392 participants, 162 with AD, 70 with other neurodegenerative diseases (NDD) with CSF biomarkers and 160 healthy controls. Plasma p-tau217 levels were measured using the Lumipulse and ALZpath SIMOA assays. The ability of p-tau217 assessed by both techniques to discriminate AD from NDD and controls was investigated using ROC analyses. Results: Both techniques showed high internal consistency of p-tau217 with similar correlation with CSF p-tau181 levels. In head-to-head comparison, Lumipulse and SIMOA showed similar diagnostic accuracy for differentiating AD from NDD (area under the curve [AUC] 0.952, 95%CI 0.927-0.978 vs 0.955, 95%CI 0.928-0.982, respectively) and HC (AUC 0.938, 95%CI 0.910-0.966 and 0.937, 95% CI0.907-0.967 for both assays). Conclusions: This study demonstrated the high precision and diagnostic accuracy of p-tau217 for the clinical diagnosis of Alzheimer's disease using either fully automated or semi-automated techniques.