Researchers have developed an innovative method for early detection of Parkinson's disease - 20 years before the first symptoms appear - paving the way for preventive treatment. Additionally, the technique could be adapted for the early diagnosis of other neurodegenerative diseases, including Alzheimer's.

Parkinson's disease is a progressive neurological disorder that primarily affects movement. It develops gradually, starting with mild symptoms that worsen over time, including tremors, muscle stiffness, and problems with balance and stability. It can also cause mood disorders and sleep disturbances. The disease is caused by the degeneration of neurons in the brain.

Parkinson's disease mainly affects the elderly and the prevalence increases with age. Approximately 1% of people over the age of 60 are affected by Parkinson's disease. Its prevalence increases to about 4% for people over 80 years old. About 10 million people are living with Parkinson's worldwide and the number of cases is increasing due to an aging population. Some studies predict that the prevalence of Parkinson's will double by 2040.

Currently, the diagnosis is mainly based on clinical symptoms such as tremors and gait dysfunctions, which usually appear at a later stage when a significant part of the dopaminergic neurons in the brain have already died. Available treatments mainly treat motor symptoms without halting disease progression.

Researchers at Tel Aviv University, in collaboration with three major Israeli medical centers and with scientists in the US and Germany, developed a new diagnostic method that combines super-resolution microscopy with computational analysis to detect protein aggregation in cells, a sign hallmark of Parkinson's disease. Protein aggregates, particularly the protein alpha-synuclein, begin to form about 15 years before Parkinson's symptoms appear.

Current diagnostic methods usually identify Parkinson's only after significant neurological damage has occurred. New technology enables detection at a much earlier stage, providing a crucial window for intervention.

"Our method can be used to identify early signs and enable preventive treatment in young people at risk of developing Parkinson's later in life," the researchers said. By identifying early cellular changes, this technique could potentially prevent further protein build-up and cell death during a person's younger years.

The study, recently published by the peer-reviewed Frontiers in Molecular Neuroscience, was led by Prof. Uri Ashery and PhD candidate Ofir Sade of Tel Aviv University.

The team used skin biopsies from individuals with and without Parkinson's disease to conduct their research. By examining these samples under a unique microscope using super-resolution imaging and advanced computational analysis, the researchers were able to map the distribution of alpha-synuclein molecules. As expected, a greater concentration of protein aggregates was found in individuals with Parkinson's, along with nerve cell damage in areas with a high concentration of this pathological protein.

With proof of concept established, the researchers plan to expand their study with support from the Michael J. Fox Foundation for Parkinson's Research. The next phase will involve analyzing skin biopsies from 90 individuals to determine the exact point at which normal amounts of protein turn into pathological aggregates.

To further improve the diagnostic process, the researchers aim to develop a machine learning algorithm capable of identifying correlations between motor and cognitive test results and microscopic findings. This algorithm will help predict the future development and severity of various pathologies associated with Parkinson's.

"Our main target population is relatives of Parkinson's patients who carry mutations that increase the risk for the disease," Ashery said. "We hope that in the coming years it will be possible to provide preventive treatments by tracking the effects of drugs under the microscope." The researchers highlight the potential application of the technology in the diagnosis of other neurodegenerative diseases associated with protein aggregates, such as Alzheimer's.

A clinical trial is already underway to test a drug designed to inhibit the formation of protein aggregates that cause Parkinson's disease. If successful, this method could revolutionize the approach to treating and preventing neurodegenerative diseases. By identifying at-risk individuals early, it may be possible to intervene before significant neurological damage occurs.

The breakthrough opens the door to a number of practical applications.

Individuals with a family history of Parkinson's or who carry related genetic mutations may be screened for signs of protein aggregation. Incorporating technology into routine health screenings, especially for individuals over a certain age or with known risk factors, can become a standard preventive measure.

If early protein build-up is detected, individuals can take preventive actions such as lifestyle modifications, dietary changes, or starting medications designed to slow the progression of the disease. The technology could lead to the identification of specific biomarkers associated with early Parkinson's, which could then be used to develop non-invasive screening tools such as blood or skin tests for wider and easier application in settings clinical.

Early intervention can delay or reduce the severity of motor symptoms such as tremors and stiffness, helping individuals maintain their independence and quality of life for a longer period.

Sade explained, “We have a wide window of up to 20 years for diagnosis and prevention, before symptoms appear. 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 accumulation and cell death./ TPS