Comparative analytical performance of multiple plasma Aβ42 and Aβ40 assays and their ability to predict positron emission tomography amyloid positivity

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

Spatially selective 2D RF inner field of view (iFOV) diffusion kurtosis imaging (DKI) of the pediatric spinal cord

Magnetic resonance based diffusion imaging has been gaining more utility and clinical relevance over the past decade. Using conventional echo planar techniques, it is possible to acquire and characterize water diffusion within the central nervous system (CNS); namely in the form of Diffusion Weighted Imaging (DWI) and Diffusion Tensor Imaging (DTI). While each modality provides valuable clinical information in terms of the presence of diffusion and its directionality, both techniques are limited to assuming an ideal Gaussian distribution for water displacement with no intermolecular interactions. This assumption neglects pathological processes that are not Gaussian therefore reducing the amount of potentially clinically relevant information. Additions to the Gaussian distribution measured by the excess kurtosis, or peakedness, of the probabilistic model provide a better understanding of the underlying cellular structure. The objective of this work is to provide mathematical and experimental evidence that Diffusion Kurtosis Imaging (DKI) can offer additional information about the micromolecular environment of the pediatric spinal cord. This is accomplished by a more thorough characterization of the nature of random water displacement within the cord. A novel DKI imaging sequence based on a tilted 2D spatially selective radio frequency pulse providing reduced field of view (FOV) imaging was developed, implemented, and optimized on a 3 Tesla MRI scanner, and tested on pediatric subjects (healthy subjects: 15; patients with spinal cord injury (SCI):5). Software was developed and validated for post processing of the DKI images and estimation of the tensor parameters. The results show statistically significant differences in mean kurtosis (p < 0.01) and radial kurtosis (p < 0.01) between healthy subjects and subjects with SCI. DKI provides incremental and novel information over conventional diffusion acquisitions when coupled with higher order estimation algorithms

Featured Articles Coalition Against Major Diseases/European Medicines Agency biomarker qualification of hippocampal volume for enrichment of clinical trials in predementia stages of Alzheimer&apos;s disease

Abstract Background: Regulatory qualification of a biomarker for a defined context of use provides scientifically robust assurances to sponsors and regulators that accelerate appropriate adoption of biomarkers into drug development. Methods: The Coalition Against Major Diseases submitted a dossier to the Scientific Advice Working Party of the European Medicines Agency requesting a qualification opinion on the use of hippocampal volume as a biomarker for enriching clinical trials in subjects with mild cognitive impairment, incorporating a scientific rationale, a literature review and a de novo analysis of Alzheimer&apos;s Disease Neuroimaging Initiative data