Detection of Alzheimer’s disease in the blood – Neuroscience News

Summary: A new blood sample test is able to measure the accumulation of Alzheimer’s-associated amyloid beta in the brain.

Source: Hokkaido University

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

Alzheimer’s disease is a neurodegenerative disease characterized by a 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 occurs primarily in people over the age of 65 and currently cannot be stopped or reversed. Therefore, Alzheimer’s disease is a major concern for countries with aging populations such as Japan.

A team of scientists from the University of Hokkaido and Toppan, led by specially appointed Associate Professor Kohei Yuyama at the Faculty of Advanced Biological Sciences, University of Hokkaido, has developed biosensor technology that can detect Aβ-binding exosomes in the blood of mice found to be Aβ accumulates in the brain.

Their research was published in the journal Alzheimer research & therapy.

When tested on mouse models, the Aβ-binding exosome Digital ICA^TM (idICA) showed that the concentration of Aβ-binding exosomes increased with increasing age of the mice. This is important because the mice used were Alzheimer’s disease model mice, in which Aβ builds up in the brain with age.

In addition to the lack of effective treatments for 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 tests 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 the buildup of Aβ in the brain is associated with Aβ-binding exosomes secreted by neurons that break down and transport Aβ to the brain’s microglial cells. Exosomes are membrane-bound sacs secreted by cells that have cell markers on their surface.

The team adapted Toppan’s proprietary Digital Invasive Cleavage Assay (Digital ICA^TM) to quantify the concentration of Aβ-binding exosomes in just 100 µL of blood. The device they developed captures molecules and particles in a sample individually in million-micron microscopic wells on a measurement chip and detects the presence or absence of fluorescent signals emitted by cleavage of the Aβ-binding exosomes.

Clinical trials of the technology are currently being conducted 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; Because it is generally applicable to exosome biomarkers, it can also be adapted for use in diagnosing other diseases.

About this news from Alzheimer’s research

Author: Sohail Keegan Pinto
Source: Hokkaido University
Contact: Sohail Keegan Pinto – University of Hokkaido
Picture: The image is in the public domain

Original research: Open access.
“Immunodigital Invasive Cleavage Assay for Analysis of Alzheimer’s Amyloid β-Linked Extracellular Vesicles” by Kohei Yuyama et al. Alzheimer research & therapy

See also

abstract

Immunodigital invasive cleavage assay for analysis of Alzheimer’s amyloid β-linked extracellular vesicles

background

The protracted preclinical stage of Alzheimer’s disease (AD) offers the opportunity to intervene early to prevent the disease; However, the lack of minimally invasive and easily detectable biomarkers and their measurement technologies remains unsolved. Extracellular vesicles (EVs) are nanoscale membrane vesicles released from a variety of cells that play important roles in cell-cell communication. Neuron-derived and ganglioside-enriched EVs capture and transport amyloid-ß protein, an important AD agent, to glial cells for degradation; this suggests that EVs affect Aβ accumulation in the brain. However, EV heterogeneity requires the use of a highly sensitive technique to measure specific EVs in biofluid. In this study, an immunodigital invasive cleavage assay (idICA) was developed to quantify target-intact EVs.

methods

EVs were captured on ganglioside GM1-specific cholera toxin B subunits (CTB)-conjugated magnetic beads and detected with a DNA-oligonucleotide-labeled Aβ antibody. Fluorescence signals for individual EVs were then counted using an invasive cleavage assay (ICA). This idICA examines the Aß-linked and GM1-containing EVs isolated from the culture supernatant of human APP-overexpressing N2a (APP-N2a) cells and APP-transgenic mouse sera.

Results

The idICA quantitatively detected Aß-bound and GM1-containing EVs isolated from culture supernatants of APP-N2a cells and sera from AD model mice. The idICA levels of Aβ-associated EVs in the blood gradually increased from 3 to 12 month old mice, consistent with the progression of Aβ accumulations in the brain of AD model mice.

Conclusions

The present results suggest that peripheral EVs harboring Aβ and GM1 reflect Aβ loading in mice. The idICA is a valuable tool for the easy quantitative detection of EVs as an accessible biomarker for preclinical AD diagnosis.