Search

Introduction: This report details the approach taken to providing a dataset allowing for analyses on the performance of recently developed assays of amyloid beta (Aβ) peptides in plasma and the extent to which they improve the prediction of amyloid positivity. Methods: Alzheimer's Disease Neuroimaging Initiative plasma samples with corresponding amyloid positron emission tomography (PET) data were run on six plasma Aβ assays. Statistical tests were performed to determine whether the plasma Aβ measures significantly improved the area under the receiver operating characteristic curve for predicting amyloid PET status compared to age and apolipoprotein E (APOE) genotype. Results: The age and APOE genotype model predicted amyloid status with an area under the curve (AUC) of 0.75. Three assays improved AUCs to 0.81, 0.81, and 0.84 (P <.05, uncorrected for multiple comparisons). Discussion: Measurement of Aβ in plasma contributes to addressing the amyloid component of the ATN (amyloid/tau/neurodegeneration) framework and could be a first step before or in place of a PET or cerebrospinal fluid screening study. Highlights: The Foundation of the National Institutes of Health Biomarkers Consortium evaluated six plasma amyloid beta (Aβ) assays using Alzheimer's Disease Neuroimaging Initiative samples.Three assays improved prediction of amyloid status over age and apolipoprotein E (APOE) genotype.Plasma Aβ42/40 predicted amyloid positron emission tomography status better than Aβ42 or Aβ40 alone. [ABSTRACT FROM AUTHOR]

Protein quality control and metabolic homeostasis are integral to maintaining cardiac function during stress; however, little is known about if or how these systems interact. Here we demonstrate that C [...]

Background: The National Institute on Aging and the Alzheimer's Association framework for classifying Alzheimer's disease (AD) utilizes measures of pathology for amyloid, tau, and neurodegeneration (ATN), that can identify participants for clinical trials. Currently, amyloid pathology is determined by costly PET or invasive CSF measurements. When applied to participant selection, these measures are associated with high screen failure rates and contribute to the high costs and long duration of recruitment of AD clinical trials. Recent reports indicate plasma amyloid beta (Aβ) peptides correlate highly with PET and CSF amyloid measures. This study aims to characterize novel assays as a screening tool that can quantify plasma Aβ peptides in a robust and reproducible manner. Method: The project team consists of representatives from pharmaceutical industry, nonprofit/patient advocacy, and academic institutions. Six plasma Aβ assays were selected to be part of the comparison: three liquid chromatography–mass spectrometry (LC‐MS/MS) assays and three immunoassays. Plasma samples with corresponding amyloid PET data were selected from ADNI n=130 (50% Aβ+): cognitively normal n=54 (37% Aβ+), mild cognitive impairment n=54 (46% Aβ+), and AD n=22 (91% Aβ+). Each participant's sample was tested in a blinded fashion on all six assays with analytical controls. Statistical tests were performed to identify which assays can significantly improve the Area Under the Receiver Operating Characteristic (AUROC) curve for predicting amyloid PET status compared to age and APOE ε4 status alone. Result: The project tested 130 samples across assays with comparison to amyloid PET. Initial results from assay providers show AUROCs to predict amyloid status at levels consistent with performance in earlier publications. A comparison of results for the various assays will be presented with respect to their ability to classify amyloid PET status and whether they add significantly to the prediction of amyloid positivity beyond age and genotype. Conclusion: Measurement of Aβ in plasma contributes to addressing the amyloid component of the ATN framework and can be a pre‐screen or a substitute for PET or CSF screening. Further clinical validation of these assays is planned to assess amyloidosis detection performance in a cognitively normal population. [ABSTRACT FROM AUTHOR]

Introduction: Blood tests have the potential to improve the accuracy of Alzheimer's disease (AD) clinical diagnosis, which will enable greater access to AD-specific treatments. This study compared leading commercial blood tests for amyloid pathology and other AD-related outcomes., Methods: Plasma samples from the Alzheimer's Disease Neuroimaging Initiative were assayed with AD blood tests from C2N Diagnostics, Fujirebio Diagnostics, ALZPath, Janssen, Roche Diagnostics, and Quanterix. Outcomes measures were amyloid positron emission tomography (PET), tau PET, cortical thickness, and dementia severity. Logistic regression models assessed the classification accuracies of individual or combined plasma biomarkers for binarized outcomes, and Spearman correlations evaluated continuous relationships between individual plasma biomarkers and continuous outcomes., Results: Measures of plasma p-tau217, either individually or in combination with other plasma biomarkers, had the strongest relationships with all AD outcomes., Discussion: This study identified the plasma biomarker analytes and assays that most accurately classified amyloid pathology and other AD-related outcomes., Highlights: Plasma p-tau217 measures most accurately classified amyloid and tau status. Plasma Aβ42/Aβ40 had relatively low accuracy in classification of amyloid status. Plasma p-tau217 measures had higher correlations with cortical thickness than NfL. Correlations of plasma biomarkers with dementia symptoms were relatively low., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: This report details the approach taken to providing a dataset allowing for analyses on the performance of recently developed assays of amyloid beta (Aβ) peptides in plasma and the extent to which they improve the prediction of amyloid positivity., Methods: Alzheimer's Disease Neuroimaging Initiative plasma samples with corresponding amyloid positron emission tomography (PET) data were run on six plasma Aβ assays. Statistical tests were performed to determine whether the plasma Aβ measures significantly improved the area under the receiver operating characteristic curve for predicting amyloid PET status compared to age and apolipoprotein E (APOE) genotype., Results: The age and APOE genotype model predicted amyloid status with an area under the curve (AUC) of 0.75. Three assays improved AUCs to 0.81, 0.81, and 0.84 (P < .05, uncorrected for multiple comparisons)., Discussion: Measurement of Aβ in plasma contributes to addressing the amyloid component of the ATN (amyloid/tau/neurodegeneration) framework and could be a first step before or in place of a PET or cerebrospinal fluid screening study., Highlights: The Foundation of the National Institutes of Health Biomarkers Consortium evaluated six plasma amyloid beta (Aβ) assays using Alzheimer's Disease Neuroimaging Initiative samples. Three assays improved prediction of amyloid status over age and apolipoprotein E (APOE) genotype. Plasma Aβ42/40 predicted amyloid positron emission tomography status better than Aβ42 or Aβ40 alone., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)