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An ultra-sensitive immunoassay detects and quantifies soluble Aβ oligomers in human plasma.


ABSTRACT:

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.

Results

Two new antibodies (71A1; 1G5) are oAβ-selective, label Aβ plaques in non-fixed AD brain sections, and potently neutralize the synaptotoxicity of AD brain-derived oAβ. The 71A1/3D6 assay showed excellent dilution linearity in CSF and plasma without matrix effects, good spike recovery, and specific immunodepletion.

Discussion

We have created a sensitive, high throughput, and inexpensive method to quantify synaptotoxic oAβ in human plasma for analyzing large cohorts of aged and AD subjects to assess the dynamics of this key pathogenic species and response to therapy.

SUBMITTER: Liu L 

PROVIDER: S-EPMC8938295 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

An ultra-sensitive immunoassay detects and quantifies soluble Aβ oligomers in human plasma.

Liu Lei L   Kwak Hyunchang H   Lawton Trebor L TL   Jin Shan-Xue SX   Meunier Angela L AL   Dang Yifan Y   Ostaszewski Beth B   Pietras Alison C AC   Stern Andrew M AM   Selkoe Dennis J DJ  

Alzheimer's & dementia : the journal of the Alzheimer's Association 20210922 6


<h4>Introduction</h4>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.<h4>Methods</h4>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)  ...[more]

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