Detection of Alzheimer’s disease in blood

Researchers from Hokkaido University and Toppan have developed a method to detect the accumulation of amyloid β in the brain, characteristic of Alzheimer’s disease, by biomarkers in blood samples.

Alzheimer’s disease is a neurodegenerative disease characterized by the 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 is mostly seen in people over the age of 65 and cannot currently be stopped or reversed. Thus, Alzheimer’s disease is a serious problem for countries with an aging population such as Japan.

A team of scientists from Hokkaido University and Toppan, led by specially appointed Associate Professor Kohei Yuyama from Hokkaido University’s Faculty of Advanced Life Sciences, has developed a biosensing technology that can detect Aβ-binding exosomes in the blood of mice, the number of which increases as Aβ accumulates in the brain. Their research was published in the journal Alzheimer’s disease research and therapy.

When tested in mouse models, Aβ binding exosome Digital ICA (idICA) showed that the concentration of Aβ-binding exosomes increased with the age of mice. This is important because they used mice with a model of Alzheimer’s disease in which Art accumulates in the brain with age.

In addition to the lack of effective treatments for Alzheimer’s disease, there are several methods of diagnosing the disease. Alzheimer’s disease can only be definitively diagnosed by direct examination of the brain, which can only be done after death. Accumulation of Aβ in the brain can be measured by analyzing cerebrospinal fluid or positron emission tomography; however, the former is an extremely invasive test that cannot be repeated, and the latter is quite expensive. Therefore, there is a need for a diagnostic test that is economical, accurate, and widely available.

Previous work by Yuyama’s group showed that Aβ accumulation in the brain is associated with Aβ-binding exosomes released from neurons that degrade and transport Aβ to brain microglia cells. Exosomes are membrane-enclosed sacs secreted by cells that have cellular markers on their surface. The team adapted Toppan’s proprietary Digital Invasive Cleavage (Digital ICA) assay 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 micrometer-sized microscopic wells on a measurement chip and detects the presence or absence of fluorescent signals emitted by the breakdown of Aβ-binding exosomes.

Clinical trials of the technology on humans are currently underway. This highly sensitive idICA technology is the first application of ICA that allows highly sensitive detection of exosomes containing specific surface molecules from a small amount of blood without the need to learn special techniques; as it is applicable to exosomal biomarkers in general, it may also be adapted for use in the diagnosis of other diseases.