Being able to explain your symptoms, as well as the perspective of a close family member or friend on symptoms and their impact on daily life, is an important part of diagnosing Alzheimer’s disease. Furthermore, Alzheimer’s disease is diagnosed based on memory and thinking skills tests administered by your doctor. Laboratory and imaging tests can help the doctor rule out other potential causes or better identify the disease causing dementia symptoms.
Researchers from Hokkaido University and Toppan have developed a method for detecting amyloid beta build-up in the brain, a symptom of Alzheimer’s disease, using biomarkers in blood samples.
Alzheimer’s disease is a neurodegenerative disease that causes the brain to gradually lose neurons and synapses. The accumulation of amyloid beta (Aβ) in the brain, where it forms plaques, is one of the primary causes of Alzheimer’s disease. Alzheimer’s disease primarily affects people over the age of 65 and cannot currently be stopped or reversed. As a result, Alzheimer’s disease is a major concern for countries with an aging population, such as Japan.
When tested on mice models, the Aβ-binding exosome Digital ICATM (idICA) showed that the concentration of Aβ-binding exosomes increased with the increase in age of the mice. This is significant as the mice used were Alzheimer’s disease model mice, where Aβ builds up in the brain with age.
A team of scientists from Hokkaido University and Toppan, led by Specially Appointed Associate Professor Kohei Yuyama at the Faculty of Advanced Life Science, Hokkaido University, have 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.
When tested on mice models, the Aβ-binding exosome Digital ICATM (idICA) showed that the concentration of Aβ-binding exosomes increased with the increase in age of the mice. This is significant as the mice used were Alzheimer’s disease model mice, where Aβ builds up in the brain with age.
In addition to the lack of effective treatments of Alzheimer’s, there are few methods to diagnose Alzheimer’s. Alzheimer’s can only be definitively diagnosed by direct examination of the brain – which can only be done 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 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.
Toppan’s proprietary Digital Invasive Cleavage Assay (Digital ICATM) was modified to measure the concentration of Aβ-binding exosomes in as little as 100 µL of blood. The device they created traps molecules and particles in a sample one at a time in a million micrometer-sized microscopic wells on a measurement chip and detects the presence or absence of fluorescent signals emitted by Aβ-binding exosome cleavage.
Human clinical trials of the technology are currently underway. This highly sensitive idICA technology is the first ICA application that allows for the highly sensitive detection of exosomes that retain specific surface molecules from a small amount of blood without the need to learn special techniques; because it is applicable to exosome biomarkers in general, it can also be adapted for use in the diagnosis of other diseases.
