New biosensor technology to detect Alzheimer's disease in the blood

New biosensor technology to detect Alzheimer's disease in the blood

Researchers from Hokkaido University and Toppan have developed a method to detect the accumulation of amyloid-β in the brain, a hallmark of Alzheimer's disease, using biomarkers in blood samples.

Alzheimer's disease is a neurodegenerative disease characterized by a gradual loss of neurons and synapses in the brain. One of the main causes of Alzheimer's disease is the accumulation of amyloid β (Aβ) in the brain, where it forms plaques. Alzheimer's disease occurs primarily in people over the age of 65 and currently cannot be stopped or reversed. Therefore, Alzheimer's disease is a major concern for countries with aging populations, such as Japan.

A team of scientists from Hokkaido University and Toppan, led by specially appointed Associate Professor Kohei Yuyama at the Faculty of Advanced Biosciences, Hokkaido University, has developed a biosensor technology that can detect Aβ-binding exosomes in the blood of mice, which manifests as Aβ accumulates in the brain. Her research was published in the journal Alzheimer’s Research & Therapy.

When tested in mouse models, the Aβ-binding exosome Digital ICATM (idICA) showed that the concentration of Aβ-binding exosomes increased as the mice aged. This is significant because the mice used were model mice of Alzheimer's disease, in which Aβ builds up in the brain with age.

In addition to the lack of effective treatments for Alzheimer's, there are few methods to diagnose Alzheimer's. Alzheimer's can only be definitively diagnosed through direct examination of the brain, which is only possible after death. Aβ accumulation in the brain can be measured by cerebrospinal fluid testing or by positron emission tomography; However, the former is an extremely invasive test that cannot be repeated, and the latter is quite expensive. Thus, there is a need for a diagnostic test that is economical, accurate and widely available.

Previous work from Yuyama's group has shown that Aβ buildup in the brain is associated with Aβ-binding exosomes secreted by neurons that degrade Aβ and transport it to the brain's microglial cells. Exosomes are membrane-bound sacs secreted by cells that have cell markers on their surface. The team adapted Toppan's proprietary Digital Invasive Cleavage Assay (Digital ICATM) to quantify the concentration of Aβ-binding exosomes in just 100 µL of blood. The device they developed captures molecules and particles in a sample individually in million-micrometer-sized microscopic wells on a measurement chip and detects the presence or absence of fluorescent signals emitted by the cleavage of the Aβ-binding exosomes.

Clinical trials of the technology are currently being conducted on humans. This highly sensitive idICA technology is the first application of ICA, enabling highly sensitive detection of exosomes that retain specific surface molecules from a small volume of blood without the need to learn special techniques; Because it is generally applicable to exosome biomarkers, it can also be adapted for use in diagnosing other diseases.

Source:

Hokkaido University

Reference:

Yuyama, K., et al. (2022) Immunodigital invasive cleavage assay for the analysis of Alzheimer's amyloid-β-bound extracellular vesicles. Alzheimer's research & therapy. doi.org/10.1186/s13195-022-01073-w.

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