Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Earlier Alzheimer's diagnosis may be possible with new imaging compound

02.11.2016

New tool detects Alzheimer's protein, may help identify brain changes, assess treatment effects

By the time unambiguous signs of memory loss and cognitive decline appear in people with Alzheimer's disease, their brains already are significantly damaged, dotted with clumps of a destructive protein known as amyloid beta. For years, scientists have sought methods and clues to help identify brain changes associated with Alzheimer's earlier in the disease process, so they can try to stop or even reverse the changes before they severely affect people's lives.


Researchers at Washington University School of Medicine in St. Louis have developed a chemical compound that detects the Alzheimer's protein amyloid beta better than current FDA-approved agents. The compound potentially may be used in brain scans to identify people in the earliest stages of Alzheimer's disease. In the image above, the compound has passed from the bloodstream of a living mouse into its brain, where it is detected by a positron emission tomography (PET) scan. Arrows indicate clumps of amyloid beta.

Credit: Ping Yan and Jin-Moo Lee

Now, researchers at Washington University School of Medicine in St. Louis have developed a chemical compound, named Fluselenamyl, that detects amyloid clumps better than current FDA-approved compounds. If a radioactive atom is incorporated into the compound, its location in a living brain can be monitored using positron emission tomography (PET) scans.

The compound, described in a paper published Nov. 2 in Scientific Reports, one of the Nature journals, potentially could be used in brain scans to identify the signs of early-stage Alzheimer's disease or to monitor response to treatment.

"Fluselenamyl is both more sensitive and likely more specific than current agents," said Vijay Sharma, PhD, a professor of radiology, of neurology and of biomedical engineering, and the study's senior author. "Using this compound, I think we can reduce false negatives, potentially do a better job of identifying people in the earliest stages of Alzheimer's disease and assess the effects of treatments."

Amyloid plaques are one of the most telltale findings in the brains of people with Alzheimer's disease. The neurons near such plaques are often dead or damaged, and this loss of brain cells is thought to account for difficulty with thinking, memory loss and confusion experienced by Alzheimer's patients.

Amyloid plaques can be either diffuse or compact. The compact kind has long been associated with the disease, but conventional wisdom has held that diffuse plaques are benign, since they can be found in the brains of elderly people without any symptoms of Alzheimer's disease, as well as the brains of those with Alzheimer's. Sharma believes that diffuse plaques may mark the earliest stages of the disease.

"It is a relatively underexplored area in the development of Alzheimer's pathology," Sharma said. "Since current approved agents don't detect diffuse plaques, there is no reliable noninvasive imaging tool to investigate this aspect in animal models or in patients. Our compound could be used to study the role of diffuse plaques."

Using human amyloid beta proteins, Sharma and colleagues showed that Fluselenamyl bound to such proteins two to 10 times better than each of the three FDA-approved imaging agents for detecting amyloid beta. In other words, Fluselenamyl detected much smaller clumps of the protein, indicating that it may be able to detect the brain changes associated with Alzheimer's disease earlier.

To determine whether Fluselenamyl can detect plaques in the brain, the researchers used the compound to stain brain slices from people who had died of Alzheimer's disease and, as controls, people of similar ages who had died of other causes. The brain slices from the Alzheimer's patients, but not the controls, were identified as containing plaques.

When a radioactive atom was incorporated into the compound, the researchers found very little interaction between Fluselenamyl and the healthy white matter in the human brain slices.

"A huge obstacle with existing state-of-the-art PET agents approved for plaque detection is that they tend to bind indiscriminately to the brain's white matter, which creates false positives on the scans," Sharma said. Nonspecific binding to other parts of the brain creates "noise," which makes it difficult to distinguish samples with plaques from those without.

A similar experiment comparing mice genetically predisposed to develop amyloid plaques with normal control mice showed the same pattern of high sensitivity for amyloid beta and low binding to healthy white matter.

Furthermore, Sharma and colleagues showed that when Fluselenamyl with the radioactive atom is injected intravenously into mice, the compound can cross the blood-brain barrier, bind to any plaques in their brains and be detected by PET scan. In mice without plaques, the compound is quickly flushed from the brain and then excreted from the body.

The next step is to move to testing in patients. Sharma already has submitted an application to the National Institutes of Health (NIH) for a phase 0 trial, to establish whether Fluselenamyl is safe for use in humans and behaves in the human body the same way it behaves in mice. Phase 0 trials involve a low dose given to a small number of people to learn how a molecule is processed in the body and how it affects the body.

"Ideally, we'd like to look at patients with very mild symptoms who are negative for Alzheimer's by PET scan to see if we can identify them using Fluselenamyl," Sharma said. "One day, we may be able to use Fluselenamyl as part of a screening test to identify segments of the population that are going to be at risk for development of Alzheimer's disease. That's the long-term goal."

Media Contact

Judy Martin Finch
martinju@wustl.edu
314-286-0105

 @WUSTLmed

http://www.medicine.wustl.edu 

Judy Martin Finch | EurekAlert!

More articles from Medical Engineering:

nachricht Smartphones as ophthalmoscopes save sight: Cost-effective telemedical eye screening of people with diabetes in India
09.07.2019 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Shorter courses of proton therapy can be just as effective as full courses prostate cancer
08.07.2019 | University of Pennsylvania School of Medicine

All articles from Medical Engineering >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: MOF@SAW: Nanoquakes and molecular sponges for weighing and separating tiny masses

Augsburg chemists and physicists report how they have succeeded in the extremely difficult separation of hydrogen and deuterium in a gas mixture.

Thanks to the Surface Acoustic Wave (SAW) technology developed here and already widely used, the University of Augsburg is internationally recognized as the...

Im Focus: Better thermal conductivity by adjusting the arrangement of atoms

Adjusting the thermal conductivity of materials is one of the challenges nanoscience is currently facing. Together with colleagues from the Netherlands and Spain, researchers from the University of Basel have shown that the atomic vibrations that determine heat generation in nanowires can be controlled through the arrangement of atoms alone. The scientists will publish the results shortly in the journal Nano Letters.

In the electronics and computer industry, components are becoming ever smaller and more powerful. However, there are problems with the heat generation. It is...

Im Focus: First-ever visualizations of electrical gating effects on electronic structure

Scientists have visualised the electronic structure in a microelectronic device for the first time, opening up opportunities for finely-tuned high performance electronic devices.

Physicists from the University of Warwick and the University of Washington have developed a technique to measure the energy and momentum of electrons in...

Im Focus: Megakaryocytes act as „bouncers“ restraining cell migration in the bone marrow

Scientists at the University Würzburg and University Hospital of Würzburg found that megakaryocytes act as “bouncers” and thus modulate bone marrow niche properties and cell migration dynamics. The study was published in July in the Journal “Haematologica”.

Hematopoiesis is the process of forming blood cells, which occurs predominantly in the bone marrow. The bone marrow produces all types of blood cells: red...

Im Focus: Artificial neural network resolves puzzles from condensed matter physics: Which is the perfect quantum theory?

For some phenomena in quantum many-body physics several competing theories exist. But which of them describes a quantum phenomenon best? A team of researchers from the Technical University of Munich (TUM) and Harvard University in the United States has now successfully deployed artificial neural networks for image analysis of quantum systems.

Is that a dog or a cat? Such a classification is a prime example of machine learning: artificial neural networks can be trained to analyze images by looking...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

Toward molecular computers: First measurement of single-molecule heat transfer

22.07.2019 | Information Technology

First impressions go a long way in the immune system

22.07.2019 | Health and Medicine

New Record: PLQE of 70.3% in lead-free halide double perovskites

22.07.2019 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>