An Ultra-sensitive Immunoassay Detects and Quantifies Soluble Aβ Oligomers in Human Plasma

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2021 Sep 22

PMID 34550630

Citations 16

Authors

Lei Liu

Hyunchang Kwak

Trebor L Lawton

Shan-Xue Jin

Angela L Meunier

Yifan Dang

Beth Ostaszewski

Alison C Pietras

Andrew M Stern

Dennis J Selkoe

Affiliations

Soon will be listed here.

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.

Citing Articles

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Aβ oligomers peak in early stages of Alzheimer's disease preceding tau pathology.

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