New diagnostic method offers hope for early intervention in Parkinson’s Disease
Researchers have developed a groundbreaking method for early detection of Parkinson’s disease — 20 years before the first symptoms appear — paving the way for preventive treatment.
Tel Aviv University
Moreover, the technique can be adapted for 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 rigidity, and problems of balance and stability. It can also bring about cognitive decline, mood disorders and sleep disturbances. The disease is caused by the degeneration of neurons in the brain.
Parkinson’s primarily affects older adults, and the prevalence increases with age. Approximately 1% of people over the age of 60 are affected by Parkinson’s disease. Its prevalence rises to about 4% for people over 80. An estimated 10 million are living with Parkinson’s globally and the number of cases is rising due to an aging population. Some studies forecast that the prevalence of Parkinson’s will double by 2040.
Currently, diagnosis is primarily based on clinical symptoms such as tremors and gait dysfunctions, which usually appear at a later stage when a significant portion of dopaminergic neurons in the brain have already died. Available treatments mostly address motor symptoms without halting disease progression.
Researchers at Tel Aviv University, in collaboration with three leading Israeli medical centers and with scientists in the US and Germany, developed a new diagnostic method combining super-resolution microscopy with computational analysis to detect protein aggregation in cells, a hallmark of Parkinson’s disease. Protein aggregates, specifically of the alpha-synuclein protein, begin forming about 15 years before Parkinson’s symptoms manifest.
Current diagnostic methods typically identify Parkinson’s only after substantial neurological damage has occurred. The new technology enables detection at a much earlier stage, offering a crucial window for intervention.
“Our method can be used to identify early signs and enable preventive treatment in young people at risk for developing Parkinson’s later on in their lives,” the researchers said. By pinpointing the initial cellular changes, this technique can potentially prevent further protein aggregation and cell death during a person’s younger years.
The study, recently published in the peer-reviewed Frontiers in Molecular Neuroscience was led by Prof. Uri Ashery and PhD candidate Ofir Sade of Tel Aviv University.
The team utilized 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 damage to nerve cells 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 pinpoint the exact point at which normal protein quantities turn into pathological aggregates.
To further enhance the diagnostic process, the researchers aim to develop a machine learning algorithm capable of identifying correlations between motor and cognitive test results and the microscopic findings. This algorithm will help predict the future development and severity of various pathologies associated with Parkinson’s.
“Our main target population are relatives of Parkinson’s patients who carry mutations that increase the risk for the disease,” said Ashery. “We hope that in coming years it will be possible to offer preventive treatments while tracking the effects of medications under the microscope.” The researchers emphasize the technology’s potential application in diagnosing other neurodegenerative diseases associated with protein aggregates, such as Alzheimer’s.
A clinical trial is already underway to test a drug designed to hinder the formation of the 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 variety of practical applications.
Individuals with a family history of Parkinson’s or who carry associated genetic mutations could be screened for signs of protein aggregation. Incorporating the technology into routine health screenings, especially for individuals over a certain age or with known risk factors, could become a standard preventive measure.
If early protein aggregation 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 can then be used to develop non-invasive screening tools such as a blood or skin test for broader, easier application in clinical settings.
Early intervention could delay or reduce the severity of motor symptoms like tremors and rigidity, helping individuals maintain their independence and quality of life for a longer period.
Sade explained, “We have an extensive time 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 aggregation and cell death.
