Introduction: People with Down syndrome (DS) often develop Alzheimer's disease (AD). Here, we asked whether ultrasensitive plasma immunoassays for a tau N-terminal fragment (NT1-tau) and Aβ isoforms predict cognitive impairment.
Methods: Plasma NT1-tau, Aβ , Aβ , and Aβ levels were measured in a longitudinal discovery cohort (N = 85 participants, 220 samples) and a cross-sectional validation cohort (N = 239).
Introduction: People with Down syndrome (DS) often develop Alzheimer disease (AD). Here we asked whether ultrasensitive plasma immunoassays for a tau N-terminal fragment (NT1-tau) and Aβ isoforms predict cognitive impairment.
Methods: Plasma NT1-tau, Aβ , Aβ , and Aβ levels were measured in a longitudinal discovery cohort (N = 85 participants, 220 samples) and a cross-sectional validation cohort (N = 239).
Importance: Alzheimer disease (AD), a neurodegenerative disease characterized by β-amyloid plaques and τ tangles in the brain, represents an unmet medical need with no fully approved therapeutics to modify disease progression.
Objective: To investigate the safety and efficacy of crenezumab, a humanized monoclonal immunoglobulin G4 antibody targeting β-amyloid oligomers, in participants with prodromal to mild (early) AD.
Design, Setting, And Participants: Two phase 3 multicenter randomized double-blind placebo-controlled parallel-group efficacy and safety studies of crenezumab in participants with early AD, CREAD and CREAD2, were initiated in 2016 and 2017, respectively, and were designed to evaluate the efficacy and safety of crenezumab in participants with early AD.
Introduction: Evidence strongly suggests that soluble oligomers of amyloid beta protein (oAβ) help initiate the pathogenic cascade of Alzheimer's disease (AD). To date, there have been no validated assays specific for detecting and quantifying oAβ in human blood.
Methods: We developed an ultrasensitive oAβ immunoassay using a novel capture antibody (71A1) with N-terminal antibody 3D6 for detection that specifically quantifies soluble oAβ in the human brain, cerebrospinal fluid (CSF), and plasma.
The availability of blood-based assays detecting Alzheimer's disease (AD) pathology should greatly accelerate AD therapeutic development and improve clinical care. This is especially true for markers that capture the risk of decline in pre-symptomatic stages of AD, as this would allow one to focus interventions on participants maximally at risk and at a stage prior to widespread synapse loss and neurodegeneration. Here we quantify plasma concentrations of an N-terminal fragment of tau (NT1) in a large, well-characterized cohort of clinically normal elderly who were followed longitudinally.
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