Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer's disease assessment.

Introduction: Plasma Aβ42/40 ratio can help predict amyloid PET status, but its clinical utility in Alzheimer's disease (AD) assessment is unclear.

Methods: Aβ42/40 ratio was measured by LC-MS/MS for 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and for 6,192 consecutive clinical specimens submitted for Aβ42/40 testing.

Results: High diagnostic sensitivity and negative predictive value (NPV) for Aβ-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aβ42/40 values for individuals with positive vs.

Diffusion MRI relates to plasma Aβ42/40 in PET negative participants without dementia.

Introduction: Magnetic resonance imaging (MRI) biomarkers are needed for indexing early biological stages of Alzheimer's disease (AD), such as plasma amyloid-β (Aβ42/40) positivity in Aβ positron emission tomography (PET) negative individuals.

Methods: Diffusion free-water (FW) MRI was acquired in individuals with normal cognition (NC) and mild cognitive impairment (MCI) with Aβ plasma-/PET- (NC = 22, MCI = 60), plasma+/PET- (NC = 5, MCI = 20), and plasma+/PET+ (AD dementia = 21) biomarker status. Gray and white matter FW and fractional anisotropy (FAt) were compared cross-sectionally and the relationships between imaging, plasma and PET biomarkers were assessed.

Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer's disease assessment.

Introduction: Plasma Aβ42/40 ratio can be used to help predict amyloid PET status, but its clinical utility in Alzheimer's disease (AD) assessment is unclear.

Methods: Aβ42/40 ratio was measured by LC-MS/MS in 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and 6,192 consecutive clinical specimens submitted for Aβ42/40 testing.

Results: High diagnostic sensitivity and negative predictive value (NPV) for Aβ-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aβ42/40 values for individuals with positive vs negative Aβ-PET results.

Antibody-Free Quantification of Serum Chromogranin A by Targeted Mass Spectrometry.

Background: Chromogranin A (CgA) is a 48 kDa protein that serves as a diagnostically sensitive, but nonspecific, serum biomarker for neuroendocrine tumors. Immunoassays for CgA are not standardized and have a narrow dynamic range, which requires dilution of concentrated specimens. We developed and validated an antibody-free, liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based method for CgA without these limitations.

High-Throughput Mass Spectrometry Assay for Quantifying β-Amyloid 40 and 42 in Cerebrospinal Fluid.

Background: The ratio of β-amyloid 1-42 (Aβ42) to Aβ40 in cerebrospinal fluid (CSF) may be useful for evaluating Alzheimer disease (AD), but quantification is limited by factors including preanalytical analyte loss. We developed an LC-MS/MS assay that limits analyte loss. Here we describe the analytical characteristics of the assay and its performance in differentiating patients with AD from non-AD dementia and healthy controls.

Profiling of proteins secreted in the bovine oviduct reveals diverse functions of this luminal microenvironment.

The oviductal microenvironment is a site for key events that involve gamete maturation, fertilization and early embryo development. Secretions into the oviductal lumen by either the lining epithelium or by transudation of plasma constituents are known to contain elements conducive for reproductive success. Although previous studies have identified some of these factors involved in reproduction, knowledge of secreted proteins in the oviductal fluid remains rudimentary with limited definition of function even in extensively studied species like cattle.

CaMKII Phosphorylation of Na(V)1.5: Novel in Vitro Sites Identified by Mass Spectrometry and Reduced S516 Phosphorylation in Human Heart Failure.

The cardiac voltage-gated sodium channel, Na(V)1.5, drives the upstroke of the cardiac action potential and is a critical determinant of myocyte excitability. Recently, calcium (Ca(2+))/calmodulin(CaM)-dependent protein kinase II (CaMKII) has emerged as a critical regulator of Na(V)1.