Dataset Information
Analytical and Clinical Performance of Amyloid-Beta Peptides Measurements in CSF of ADNIGO/2 Participants by an LC-MS/MS Reference Method.
Ontology highlight
ABSTRACT: Background
Cerebrospinal fluid (CSF) amyloid-?1-42 (A?42) reliably detects brain amyloidosis based on its high concordance with plaque burden at autopsy and with amyloid positron emission tomography (PET) ligand retention observed in several studies. Low CSF A?42 concentrations in normal aging and dementia are associated with the presence of fibrillary A? across brain regions detected by amyloid PET imaging.Methods
An LC-MS/MS reference method for A?42, modified by adding A?40 and A?38 peptides to calibrators, was used to analyze 1445 CSF samples from ADNIGO/2 participants. Seventy runs were completed using 2 different lots of calibrators. For preparation of A?42 calibrators and controls spiking solution, reference A?42 standard with certified concentration was obtained from EC-JRC-IRMM (Belgium). A?40 and A?38 standards were purchased from rPeptide. A?42 calibrators' accuracy was established using CSF-based A?42 Certified Reference Materials (CRM).Results
CRM-adjusted A?42 calibrator concentrations were calculated using the regression equation Y (CRM-adjusted) = 0.89X (calibrators) + 32.6. Control samples and CSF pools yielded imprecision ranging from 6.5 to 10.2% (A?42) and 2.2 to 7.0% (A?40). None of the CSF pools showed statistically significant differences in A?42 concentrations across 2 different calibrator lots. Comparison of A?42 with A?42/A?40 showed that the ratio improved concordance with concurrent [18F]-florbetapir PET as a measure of fibrillar A? (n?=?766) from 81 to 88%.Conclusions
Long-term performance assessment substantiates our modified LC-MS/MS reference method for 3 A? peptides. The improved diagnostic performance of the CSF ratio A?42/A?40 suggests that A?42 and A?40 should be measured together and supports the need for an A?40 CRM.
SUBMITTER: Korecka M
PROVIDER: S-EPMC7108496 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
Publications
Analytical and Clinical Performance of Amyloid-Beta Peptides Measurements in CSF of ADNIGO/2 Participants by an LC-MS/MS Reference Method.
Clinical chemistry 20200401 4
<h4>Background</h4>Cerebrospinal fluid (CSF) amyloid-β1-42 (Aβ42) reliably detects brain amyloidosis based on its high concordance with plaque burden at autopsy and with amyloid positron emission tomography (PET) ligand retention observed in several studies. Low CSF Aβ42 concentrations in normal aging and dementia are associated with the presence of fibrillary Aβ across brain regions detected by amyloid PET imaging.<h4>Methods</h4>An LC-MS/MS reference method for Aβ42, modified by adding Aβ40 an ...[more]