To identify key pathogenic proteins in Alzheimer's disease, Harvard scientists develop important detection tools

▎Edited by WuXi AppTec's content team In the brains of patients with Alzheimer's disease (AD), the deposition of a large amount of amyloid β (Aβ) is a hallmark pathological phenomenon
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However, many research evidences suggest that small-scale aggregates composed of a small amount of Aβ, namely soluble Aβ oligomers, are highly toxic to nerve synapses and are the main toxic substance in Alzheimer’s disease.

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Recently, scientists have developed a sensitive detection method specifically designed to identify and quantify Aβ oligomers in the human brain, cerebrospinal fluid, and blood
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The birth of this tool will help confirm the potential key pathogenic mechanism of Aβ oligomers in the AD mechanism
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▲Related research was published in the professional academic journal Alzheimer's & Dementia.
This detection method was developed by a research team led by Professor Dennis Selkoe of Harvard Medical School and a biotechnology startup company Abyssinia Biologics
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Specifically, the researchers established an assay method called "sandwich immunoassay", the key to which is the use of two new specific antibodies 71A1 and 1G5 for the selective recognition of Aβ in the form of oligomers
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After the antibody 71A1 or 1G5 "grabs" the Aβ oligomer, another antibody 3D6 binds to it to "clamp" the Aβ oligomer, and the antibody 3D6 is connected to a fluorescent label to make quantitative detection
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▲Taking 71A1 antibody as an example, the principle of sandwich immunoassay for Aβ oligomers (picture source: reference [1]) According to the researchers, due to the use of new antibodies that are more selective for Aβ oligomers, Compared with the old method they designed with similar principles, the sensitivity of the new method is 100 times higher
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In this way, for the first time, people have realized the detection of blood samples instead of using cerebrospinal fluid samples as before
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Blood test is obviously much more convenient than taking cerebrospinal fluid, so this method is expected to become a routine method for measuring Aβ oligomers
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With this method of detecting Aβ oligomers, the researchers pointed out that it can be applied to a large number of patients or trial cohorts at risk of disease to monitor the dynamic changes of Aβ oligomers in the early and course of Alzheimer's disease.

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Professor Kaj Blennow of the University of Gothenburg in Sweden commented: "Exploring the pathophysiological role of Aβ oligomers in AD patients and longitudinal studies of the elderly who have not yet developed the disease but are at risk will serve as an important tool
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Image Source: 123RF researchers introduced that they will further test whether this detection tool can distinguish Alzheimer patients from healthy people, distinguish between amyloid-positive and negative test participants, and Aβ oligomers in their follow-up work Whether it is related to other biomarkers of Alzheimer's disease
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These findings will provide clues for the diagnosis and treatment of Alzheimer's disease
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In addition, Dr.
Liu Lei, the first author of the research paper, introduced the new antibody 71A1 they used It can effectively neutralize Aβ oligomers produced in the brain and reduce the toxicity of these proteins to nerve synapses.
Therefore, 71A1 has the potential to be developed as an immunotherapy for the treatment of AD.
They are testing this on Alzheimer's disease model mice.
Ideas
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We look forward to the emergence of new ways to benefit patients with Alzheimer's disease as soon as possible
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Reference materials: [1] Lei Liu et al.
, (2021) An ultra-sensitive immunoassay detects and quantifies soluble Aβ oligomers in human plasma.
DOI: 10.
1002/alz.
12457[2] First Plasma Assay for Oligomeric Aβ Binds Synaptotoxic Species.
Retrieved Oct.
9, 2021 from https://