Tag Archives: neurons

Detecting Alzheimer’s disease in the blood using Digital ICA

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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

Child abuse affects brain wiring

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Impaired neural connections may explain profound and long-lasting effects of traumatic experiences during childhood

  • For the first time, researchers have been able to see changes in the neural structures in specific areas of the brains of people who suffered severe abuse as children.
  • Difficulties associated with severe childhood abuse include increased risks of psychiatric disorders such as depression, as well as high levels of impulsivity, aggressivity, anxiety, more frequent substance abuse, and suicide.
    Severe, non-random physical and/or sexual child abuse affects between 5-15 % of all children under the age of 15 in the Western world.
  • Researchers from the McGill Group for Suicide Studies, based at the Douglas Mental Health University Institute and McGill University’s Department of Psychiatry, have just published research in the American Journal of Psychiatry that suggests that the long-lasting effects of traumatic childhood experiences, like severe abuse, may be due to an impaired structure and functioning of cells in the anterior cingulate cortex. This is a part of the brain which plays an important role in the regulation of emotions and mood.
  • The researchers believe that these changes may contribute to the emergence of depressive disorders and suicidal behaviour.

Crucial insulation for nerve fibres builds up during first two decades of life

For the optimal function and organization of the brain, electrical signals used by neurons may need to travel over long distances to communicate with cells in other regions. The longer axons of this kind are generally covered by a fatty coating called myelin. Myelin sheaths protect the axons and help them to conduct electrical signals more efficiently. Myelin builds up progressively (in a process known as myelination) mainly during childhood, and then continue to mature until early adulthood.

Earlier studies had shown significant abnormalities in the white matter in the brains of people who had experienced child abuse. (White matter is mostly made up of billions of myelinated nerve fibres stacked together.) But, because these observations were made by looking at the brains of living people using MRI, it was impossible to gain a clear picture of the white matter cells and molecules that were affected.

To gain a clearer picture of the microscopic changes which occur in the brains of adults who have experienced child abuse, and thanks to the availability of brain samples from the Douglas-Bell Canada Brain Bank (where, as well as the brain matter itself there is a lot of information about the lives of their donors) the researchers were able to compare post-mortem brain samples from three different groups of adults: people who had committed suicide who suffered from depression and had a history of severe childhood abuse (27 individuals); people with depression who had committed suicide but who had no history of being abused as children (25 individuals); and brain tissue from a third group of people who had neither psychiatric illnesses nor a history of child abuse (26 people).

Impaired neural connectivity may affect the regulation of emotions

The researchers discovered that the thickness of the myelin coating of a significant proportion of the nerve fibres was reduced ONLY in the brains of those who had suffered from child abuse. They also found underlying molecular alterations that selectively affect the cells that are responsible for myelin generation and maintenance. Finally, they found increases in the diameters of some of the largest axons among only this group and they speculate that together, these changes may alter functional coupling between the cingulate cortex and subcortical structures such as the amygdala and nucleus accumbens (areas of the brain linked respectively to emotional regulation and to reward and satisfaction) and contribute to altered emotional processing in people who have been abused during childhood.

The researchers conclude that adversity in early life may lastingly disrupt a range of neural functions in the anterior cingulate cortex. And while they don’t yet know where in the brain and when during development, and how, at a molecular level these effects are sufficient to have an impact on the regulation of emotions and attachment, they are now planning to explore this in further research.