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

In the brains of patients with Alzheimer's disease (AD), the deposition of large amounts of amyloid β (Aβ) is a hallmark pathological phenomenon
.

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.

Recently, scientists have developed a sensitive detection method specifically designed to identify and quantify Aβ oligomers in the human brain, cerebrospinal fluid, and blood
.

The birth of this tool will help confirm the potential key pathogenic mechanism of Aβ oligomers in the AD mechanism

This detection method was developed by a research team led by Professor Dennis Selkoe of Harvard Medical School in cooperation with the biotechnology startup Abyssinia Biologics
.

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
.

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

▲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 switch to a new type of antibody that is more selective for Aβ oligomers, the sensitivity of the new method is 100 times higher than that of their previous old method designed with similar principles
.

In this way, for the first time, people have realized the detection of blood samples instead of using cerebrospinal fluid samples as before

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
.

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.

According to the researchers, they will further test whether this detection tool can distinguish Alzheimer patients from healthy people, distinguish test participants with amyloid positive and negative, and Aβ oligomers from Alzheimer’s in their follow-up work.
Are there any links to other biomarkers of Haimer's disease
?

Note: The original text has been deleted

Reference materials:

[1] Lei Liu et al.

, (2021) An ultra-sensitive immunoassay detects and quantifies soluble Aβ oligomers in human plasma.

[2] First Plasma Assay for Oligomeric Aβ Binds Synaptotoxic Species.