Breakthrough could diagnose and prevent Parkinson’s disease 20 years before symptoms start

A new breakthrough in early detection for Parkinson’s disease could revolutionize how the disease is diagnosed and treated, potentially offering up to a 20-year window before the first symptoms even appear.

Researchers at Tel Aviv University, in collaboration with three major Israeli medical centers, have developed a method that uses advanced microscopy techniques to identify early signs of Parkinson’s. This innovative approach could dramatically improve treatment options, or even prevent the onset of the disease altogether.

Parkinson’s disease is a devastating condition that affects about 8.5 million people worldwide. It is the second most prevalent neurodegenerative disease after Alzheimer's, with 1,200 new cases diagnosed in Israel each year.

Parkinson’s is marked by the destruction of dopamine-producing neurons in the brain’s Substantia Nigra region, leading to symptoms like tremors, rigidity, and gait problems. These motor symptoms generally don’t appear until the disease is well advanced, often when 50 to 80 percent of the dopamine neurons are already destroyed. As a result, current treatments are limited to addressing motor issues rather than slowing or preventing neuron loss.

Led by Professor Uri Ashery and PhD candidate Ofir Sade, the Tel Aviv research team aimed to develop a diagnostic tool that would detect the disease at a much earlier stage. The tool could enable doctors to intervene when the brain cells are still treatable, opening the door to therapies that may prevent further damage.

Their method, which combines super-resolution microscopy with computational analysis, allows scientists to precisely map the molecular structure of protein aggregates associated with Parkinson's. This could provide a window of up to two decades to intervene before symptoms emerge.

One of the hallmarks of Parkinson’s disease is the buildup of a protein called alpha-synuclein, which begins to aggregate in cells long before motor symptoms appear. "We have an extensive time window of up to 20 years for diagnosis and prevention before symptoms appear," explains Sade. "If we can identify the process at an early stage, in people who are 30, 40, or 50 years old, we may be able to prevent further protein aggregation and cell death."

The team has shown that alpha-synuclein aggregates not only in the brain but also in other areas of the body, such as the skin and digestive system. In their study, the researchers examined skin biopsies from 14 individuals—half with Parkinson’s disease and half without.

Using their advanced super-resolution microscopy technique, they were able to map the distribution of alpha-synuclein molecules and found that people with Parkinson’s had significantly more protein aggregates than those without the disease. They also observed damage to the nerve cells in areas with a high concentration of the pathological protein.

"The results were what we expected, but they also opened the door to further exploration," says Sade. He notes that by applying this method, it may be possible to identify at what point a normal quantity of alpha-synuclein transforms into dangerous aggregates. This is crucial for understanding how the disease progresses and could help target therapies to stop the aggregation process before it becomes irreversible.

With this initial success, the researchers plan to expand their study, increasing the number of participants from 14 to 90, to better pinpoint when normal protein behavior turns pathological. Supported by the Michael J. Fox Foundation for Parkinson’s Research, they will collect skin biopsies from 45 people with Parkinson’s and 45 without, refining their technique to identify earlier and more subtle signs of disease.

As part of the next phase, the researchers will also collaborate with Professor Lior Wolf from Tel Aviv University's School of Computer Science to develop a machine-learning algorithm. This algorithm will analyze the findings from both motor and cognitive tests to predict the future severity of Parkinson’s disease in individuals based on early microscopic signs.

The research holds tremendous promise, not only for Parkinson’s but for other neurodegenerative diseases that involve protein aggregation, like Alzheimer's. "We hope that in coming years it will be possible to offer preventive treatments while tracking the effects of medications under the microscope," Professor Ashery adds.

The team has already started a clinical trial to test a drug that may prevent the formation of alpha-synuclein aggregates, a significant step toward preventing the onset of Parkinson’s in high-risk individuals.

Their work is particularly focused on people who carry genetic mutations that increase the likelihood of developing the disease. Certain mutations are more common in specific populations, such as Ashkenazi Jews, who are at a higher risk for Parkinson’s due to these genetic factors.

The team is already identifying relatives of Parkinson’s patients who may benefit from this early diagnostic tool, enabling preventative treatment years before the disease would normally be detected.

With further development, this technology could one day make it possible to diagnose Parkinson’s, and other neurodegenerative diseases, long before symptoms surface. This could transform how doctors approach these illnesses, moving from a reactive model to a proactive one, where treatments are administered years in advance to prevent the severe and irreversible damage these diseases cause.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

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