Amyloid-β Binding Exosomes in Blood Samples as a Biomarker of Alzheimer's Disease
Several research groups are in the later stages of developing a number of different approaches to blood-based assays to detect the early stages of Alzheimer's disease, or at least the buildup of amyloid-β in the brain that takes place over a span of years, long before symptoms manifest. Early detection should lead to means of early intervention, always a good deal easier than later intervention. Here, researchers outline a novel approach to detection of amyloid-β burden, finding amyloid-β levels correlated with those of a form of exosome carried in the circulation.
One of the primary 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 individuals over 65 years of age, and cannot currently be stopped or reversed. 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 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 established a way 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 cleaving of the Aβ-binding exosomes.
When tested on mouse models, the Aβ-binding exosome assay 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. Clinical trials of the technology are currently underway in humans.
Link: https://www.global.hokudai.ac.jp/blog/detecting-alzheimers-disease-in-the-blood/