Handheld device may help spot markers

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  • Finding biomarkers of Alzheimer’s or Parkinson’s disease that can be detected via bodily fluids such as saliva, urine, and blood could help researchers identify and develop new drugs and treatments.
  • A group of researchers last year developed a wireless device that can detect a tiny number of molecules, specifically for SARS-CoV-2 strains.
  • Now, they have shown their device can be adapted to detect molecules linked to Alzheimer’s disease and Parkinson’s disease.

A team of researchers based at the University of California, San Diego, who developed a wireless, handheld device to detect specific biomolecules, have now shown their device can detect molecules associated with Alzheimer’s disease and Parkinson’s disease.

The device was originally developed to detect SARS-CoV-2, the virus that causes COVID-19. It works using aptamers, or short strands of DNA or RNA that bind only to specific molecules. When binding takes place on the single-atom-thick graphene layer in the machine, electrical energy is able to flow, which creates a positive reading confirming the molecule has been detected.

This previous study showed their device was capable of detecting specific strains of the SARS-CoV-2 virus, when only a very small number of viruses were present.

In the most recent research by this team, researchers have shown that their device is capable of detecting different forms of beta-amyloid and tau, peptides that characterize Alzheimer’s disease, and α-synuclein—a peptide found in higher levels in the brains of people with Parkinson’s disease.

They used samples taken from the autopsied brains of deceased patients to test the device’s ability to detect these molecules.

Their findings were published in Biophysics and Computational Biology.

The number of people living with Alzheimer’s disease in the U.S. could rise from 6.7 million people today, to 13.8 million people in 2060 if no significant breakthrough is made.

Breakthroughs are needed in developing treatments, but also diagnosis, as it has proven challenging to design clinical trials demonstrating the efficacy of drugs, with cohorts of patients already exhibiting symptoms of the disease.

Currently, Alzheimer’s disease is detected by using a combination of neurocognitive testing, MRI, and PET scanning, often after the onset of symptoms, including cognitive decline.

PET scans work by detecting the presence of amyloid plaques, which are formed when a peptide known as beta-amyloid, builds up due to tangles it forms with another peptide, tau. These tangles are thought to interrupt nerve cell signaling in the brain, which leads to the cognitive decline seen in Alzheimer’s disease patients.

The presence of these plaques in the brains of people with Alzheimer’s disease means that most researchers focus on the presence and actions of these peptides and the mechanisms that might be underpinning them.

However, isolating these peptides remains complex and potentially invasive due to their presence in the brain.

The study results showed that the device the researchers had developed was able to detect different forms of these beta-amyloid peptides at low concentrations with high degrees of accuracy.

“What we saw in this paper is that the amount of beta-amyloid that goes into the brain in the saliva is almost 1,000 times more than what is the sensitivity of our system,” lead author Dr. Ratnesh Lal told Medical News Today in an interview.

He said the strength of the device they had developed was due to the sensitivity of the electrical system, as there was no cross-reactivity that can confuse results.

The authors of the paper say that they want to see whether or not they can detect these molecules in blood plasma and cerebrospinal fluid with the device, and then saliva and urine next.

There is still research to be done into the best type of biomarkers to detect Alzheimer’s disease in different types of body fluid, said Dr. Thomas K Karikari, assistant professor of psychiatry at the University of Pittsburgh, who researches biomarkers for Alzheimer’s disease and was not involved in the research.

There are also challenges associated with carrying out standardized pathology tests on amyloid and tau, to get consistent enough results that false positives and negatives are avoided.

Amyloid is difficult to isolate and work with as it is so sticky in its nature. The blood-brain barrier also means that most of the changes seen in the brain are not necessarily reflected in blood concentrations or those concentrations seen in different tissues outside of the brain. In other words, how can you tell if these biomarkers have come from the brain, and not somewhere else in the body?

Dr. Karikari told MNT that his own research had looked at the phosphorylation patterns on Alzheimer’s specific tau-peptides to determine which specific molecules could be determined to have come from the brain and present in different concentrations in Alzheimer’s patients compared to a non-disease population.

Previous research of his had shown that tau binding is particularly strong around the salivary gland, and “[We] showed at that time that there was no difference for saliva between the diagnostic group. So we actually ended that at that point,” said Dr. Karikari, as it meant tau in saliva was not a good biomarker for Alzheimer’s disease as it would not necessarily be from the brain.

Now, however, he said that work has been done to determine the phosphorylation patterns on tau that characterize Alzheimer’s disease, “so hopefully we can go back and be able to characterize the tau from the saliva much better.”

Dr. Karikari said less research had been done on urine, and there were particular challenges associated with collecting urine from incontinent elderly patients.

The authors of the paper say they plan on applying for FDA approval for the device in the next five or six months with a goal to have the device on the market in a year.

Read the full article here

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