Detecting Alzheimer’s disease in the blood using Digital ICA

Researchers from Hokkaido University and Toppan 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.

Alzheimer’s disease is a neurodegenerative disease, characterised by a gradual loss of neurons and synapses in the brain. 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. Thus, Alzheimer’s disease is a major concern for nations with ageing 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 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.

Alzheimer’s disease

Alzheimer’s disease model mice (Photo: Kohei Yuyama)./CREDIT:Kohei Yuyama

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. The team adapted Toppan’s proprietary Digital Invasive Cleavage Assay (Digital ICATM) 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.

Clinical trials of the technology are currently underway in humans. This highly sensitive idICA technology is the first application of 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.

Noninvasive eye scan could detect key signs of Alzheimer’s years before patients show symptoms

Air pollution is more dangerous for women than men: Study

The impact of breathing diesel exhaust fumes may be more severe for females than males, according to new research that will be presented at the European Respiratory Society International Congress in Barcelona, Spain [1].

Researchers looked for changes in people’s blood brought about by exposure to diesel exhaust. In both females and males, they found changes in components of the blood related to inflammation, infection and cardiovascular disease, but they found more changes in females than males.

The research was presented by Dr Hemshekhar Mahadevappa, from the University of Manitoba, Winnipeg, Canada and was a collaboration between two research groups led by Professor Neeloffer Mookherjee at the University of Manitoba and Professor Chris Carlsten at the University of British Columbia, Vancouver, Canada. Dr Mahadevappa told the Congress: “We already know that there are sex differences in lung diseases such as asthma and respiratory infections.

Air pollution/Photo:en.wikipedia.org

Research showed that breathing diesel exhaust creates inflammation in the lungs and has an impact on how the body deals with respiratory infections. In this study, we wanted to look for any effects in the blood and how these differ in females and males.”

The study involved ten volunteers, five female and five male, who were all healthy non-smokers. Each volunteer spent four hours breathing filtered air and four hours breathing air containing diesel exhaust fumes at three different concentrations – 20, 50 and 150 micrograms of fine particulate matter (PM2.5) per cubic metre – with a four-week break in between each exposure.

Volunteers donated blood samples 24 hours after each exposure and the researchers made detailed examinations of the volunteers’ blood plasma. Plasma is the liquid component of the blood that carries blood cells as well as hundreds of proteins and other molecules around the body. Using a well-established analysis technology called liquid chromatography–mass spectrometry, the researchers looked for changes in the levels of different proteins following exposure to diesel exhaust and compared the changes in females and males.

Airpollution/Photo:en.wikipedia.org

Comparing the plasma samples, the researchers found levels of 90 proteins that were distinctly different between female and male volunteers following exposure to diesel exhaust. Among the proteins that differed between females and males, were some that are known to play a role in inflammation, damage repair, blood clotting, cardiovascular disease and the immune system. Some of these differences became clearer when volunteers were exposed to the higher levels of diesel exhaust.

Professor Mookherjee explained: “These are preliminary findings, however they show that exposure to diesel exhaust has different effects in female bodies compared to male and that could indicate that air pollution is more dangerous for females than males.

“This is important as respiratory diseases such as asthma are known to effect females and males differently, with females more likely to suffer severe asthma that does not respond to treatments. Therefore, we need to know a lot more about how females and males respond to air pollution and what this means for preventing, diagnosing and treating their respiratory disease.”

Air pollution/photo:en.wikipedia.org

Professor Zorana Andersen from the University of Copenhagen, Denmark, is Chair of the European Respiratory Society Environment and Health Committee and was not involved in the research. She said: “We know that exposure to air pollution, especially diesel exhaust, is a major risk factor in diseases such as asthma and chronic obstructive pulmonary disease. There is very little we can do as individuals to avoid beathing polluted air, so we need governments to set and enforce limits on air pollutants.