Alzheimer's biomarkers detected in blood samples

Japanese researchers have developed a method to detect build-up of amyloid β in the brain, a characteristic of Alzheimer’s disease, from biomarkers in blood samples.

One of the primary causes of Alzheimer’s disease is the accumulation of amyloid β (Aβ) in the brain, where it forms plaques. In terms of diagnostics, 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.

Scientists from Hokkaido University and the Toppan Technical Research Institute, led by Hokkaido’s Associate Professor Kohei Yuyama, developed a biosensing technology that can detect Aβ-binding exosomes in the blood of mice, which increase as Aβ accumulates in the brain. Their research was published in the journal Alzheimer’s Research & Therapy.

Previous work by Yuyama’s group has shown that Aβ build-up in the brain is associated with Aβ-binding exosomes secreted from neurons, which degrade and transport Aβ to the microglial cells of the brain. Exosomes are membrane-enclosed sacs secreted by cells that possess cell markers on their surface. The team adapted Toppan’s proprietary Digital Invasive Cleavage Assay (Digital ICA) to quantify the concentration of Aβ-binding exosomes in as little as 100 µL of blood. The device they developed traps molecules and particles in a sample one by one in a million micrometre-sized microscopic wells on a measurement chip and detects the presence or absence of fluorescent signals emitted by the cleaving of the Aβ-binding exosomes.

When tested on mice models, the Aβ-binding exosome Digital ICA (idICA) showed that the concentration of Aβ-binding exosomes increased with the increase in age of the mice; in Alzheimer’s disease model mice, Aβ builds up in the brain with age. Clinical trials of the technology are currently underway in humans.

The highly sensitive idICA technology is the first application of the ICA that enables highly sensitive detection of exosomes that retain specific surface molecules from a small amount of blood without the need to learn special techniques. As it is applicable to exosome biomarkers in general, it can also be adapted for use in the diagnosis of other diseases.

Image credit: iStock.com/Sewcream

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