- Researchers have developed a new biosensor that can detect structural changes in proteins indicative of neurodegenerative conditions, such as Alzheimer’s and Parkinson’s disease.
- The sensor could aid early diagnosis of various conditions and help personalize treatment options.
- Further tests are needed to understand how accurate the biosensor is in real-life settings.
Neurodegenerative conditions occur when nerve cells lose function and die. The accumulation of misfolded proteins in the brain appears to be a common feature of some of these conditions.
The most common neurodegenerative conditions are Alzheimer’s disease, which is estimated to affect 6.7 million people in the United States, and Parkinson’s disease, which affects nearly a million people in the U.S.
Most neurodegenerative conditions begin 10–15 years before clinical symptoms occur. However, early intervention is often hampered by a lack of reliable early diagnostic tools. Furthermore, they are often misdiagnosed due to overlapping symptoms among the conditions.
While current diagnostic methods identify and quantify protein levels, they are insensitive to their structural changes.
Structural changes are key to understanding how much neurodegeneration has occurred as misfolded proteins in multiple conditions — including Parkinson’s and Alzheimer’s — undergo structural changes and combine into oligomers and later into fibrils.
Oligomers are highly unstable, disordered structures, whereas fibrils are more stable and organized molecules.
Dr. Jennifer Bramen, a senior research scientist at the Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, CA, told Medical News Today:
“Current efforts are focused on exploring therapeutic approaches that target protein misfolding. However, the lack of biomarkers to monitor disease progression and assess treatment response poses a significant challenge to research and development in this field.”
Methods to detect different stages of protein folding could enhance diagnostic tests for neurodegenerative conditions.
New biosensor could identify toxic proteins
Recently, researchers developed a biosensor called ImmunoSEIRA that can detect and identify misfolded proteins linked to different neurodegenerative conditions.
They hope that the new technology will improve early detection and monitoring for neurodegenerative conditions, as well as help assess treatment options at various stages of disease progression.
“By combining the ImmunoSEIRA sensor with AI analysis, we can now detect and quantify oligomers and fibrils, which is unprecedented and not possible with the existing detection strategies,” Deepthy Kaungal, doctoral assistant in the Bionanophotonic Systems Laboratory at the EPFL, the Swiss Federal Institute of Technology in Lausanne, Switzerland, the lead author of the study, told MNT.
The study was published in Science Advances.
Biosensor acts as ‘molecular detective’
When asked how ImmunoSEIRA works, Kaungal said it acts as a “molecular detective.”
The researchers equipped ImmunoSEIRA with an immunoassay to ensure it assesses the correct molecules. An immunoassay is a biochemical test that uses antibodies to latch onto specific molecules — in this case, those abnormal proteins linked to Parkinson’s disease and Alzheimer’s disease.
Once antibody and protein complexes are captured, arrays of nanometer-sized gold structures known as “nanorods” amplify their unique “fingerprints” so they can be mapped via surface-enhanced infrared absorption (SEIRA) spectroscopy, an “infrared detection system” used to identify and analyze biomarkers.
“[At this point], information from the scan is fed into a machine-learning (AI) based algorithm which gives information about the types of misfolded protein that are present,” Dr. Charles Munyon, a functional neurosurgeon with Novant Health in Charlotte, NC, not involved in the study, told MNT.
Already, the researchers have tested ImmunoSEIRA in biofluids like cerebrospinal fluid from clinical settings. In doing so, they were able to identify signatures from abnormal protein fibrils.
Better diagnostic tools for the future
“This approach gives more information about the type of misfolded protein present, which tells us significantly more about the stage of the disease that the patient is currently in,” said Dr. Munyon.
Kaungal added that ImmunoSERIA could also improve diagnostic accuracy as, unlike most biomarker studies and diagnostics that measure levels of one protein, their technology allows the simultaneous measurement of multiple biomarkers.
“Our method relies on the use of small volumes of biofluids, which increases the number of analyses one can perform from the same patient sample,” she explained.
Tool may only screen for one condition at a time
Kaungal noted that the study’s main limitation is that ImmunoSEIRA has yet to be applied to clinical samples, although they plan to do this soon.
“We will need to [optimize] the sensor first and then validate it in comparison with existing methods to benchmark its performance,” she said.
When asked about other limitations, Dr. Munyon said that while initial tests in patients appear promising, it is hard to comment on its overall ability to discriminate between disease stages until further testing is done.
“While this technique should allow for screening for additional diseases besides Parkinson’s and Alzheimer’s, it may not be able to screen for more than one disease at a time unless multiple assays are run on the same specimen,” he added.
MNT also spoke with Dr. Howard Pratt, a board-certified psychiatrist and behavioral health medical director at Community Health of South Florida, not involved in the study, about its limitations.
“One of the limitations this research may face has to do with how such innovations are received by the medical community,” said Dr. Pratt.
He noted that physicians tend to remain cautious and skeptical about the reliability of new technologies prior to their widespread acceptance.
“As a physician, you never want to be the first or last person to implement something in your practice,” he said. “Even if the test turns out to be very accurate and even superior to the current gold standard you may still see uneven adoption of it, with some embracing it and others remaining cautious.”
“We might forgive an error in judgment in diagnosis made by a doctor, or by an already established test, but people are less likely to forgive an algorithm,” he added.
A diagnostic tool still far in the future
Kaungal noted that their findings might help with making earlier diagnoses, facilitate ways to group patients based on their specific condition, and personalize treatments according to both the chemical makeup and structure of protein clumps.
Dr. Munyon added that while the findings are exciting from a technological standpoint, it is crucial for the public to understand that this is not a treatment and will likely take some time to become widely used.
“Alzheimer’s disease and Parkinson’s disease remain very common, and unfortunately very difficult to treat and devastating in their impact. While every new development helps, we still appear to be a long way away from being able to significantly slow either disease, let alone cure them,” he concluded.
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