Genetic analysis of blood sample could offer a non-invasive way for early Parkinson’s diagnosis

The genetic analysis of a blood sample could become a tool for the early diagnosis of Parkinson's disease, according to an exploratory study led by researchers from the Miguel Hernández University of Elche (UMH). Although not yet available for clinical use, the method was tested in newly diagnosed patients and proved effective, offering a non-invasive way to detect and monitor disease progression before major symptoms appear.

The results, published in the journal Neurotherapeutics, stem from the collaboration between scientists from the Institute of Neurosciences (a joint UMH-CSIC center), the Institute for Health and Biomedical Research of Alicante (ISABIAL), the Carlos III Health Institute, and Madrid's Hospital 12 de Octubre.

Parkinson's disease affects around 12 million people worldwide. It is the second most common neurodegenerative disorder and one of the leading causes of neurological disability. One of the most significant challenges in Parkinson's research is achieving a diagnosis before severe motor symptoms emerge.

Currently, diagnosis begins with a clinical examination when visible symptoms appear. "However, tremors occur when neurological damage is already advanced and may be mistaken for other disorders," explains UMH Professor Jorge Manzanares, who led the study. "Until recently, the only definitive diagnosis came from post-mortem tissue analysis, but it is crucial to develop fast, minimally invasive methods that detect the disease earlier."

The UMH team's approach requires only a blood draw. The analysis, performed with equipment already available in many hospital laboratories, identifies genetic alterations associated with the disease in its earliest stages.

The key lies in genetically analyzing a type of immune cells called peripheral blood mononuclear cells."

Francisco Navarrete, UMH Professor, first author of the study

He notes that, as with all cells, they contain genetic information, but not all genes are active at all times. Some genes switch on or off depending on the body's needs - for example, in response to an infection or during the development of a disease.

Using sequencing and bioinformatic analysis, the team identified more than twenty genes whose activity was altered in patients with Parkinson's disease who had not yet received pharmacological treatment. "These changes are not seen in healthy individuals," says Marina Guillot, a predoctoral researcher who conducted the gene expression analyses together with CSIC scientist José P. López-Atalaya, adding: "This suggests they could serve as reliable diagnostic markers and also provide clues to the biological mechanisms underlying disease development and progression."

In total, 22 genes showed differential expression between Parkinson's patients and healthy volunteers. Some are involved in immune responses, supporting the hypothesis that inflammation and the immune system play a role in the disease's development. Others are linked to molecular transport within brain tissue and iron homeostasis - processes previously associated with neurotoxicity.

Beyond gene expression, the researchers detected changes in cellular pathways associated with survival, inflammation, cell death, and the composition of immune cells. "We still do not fully understand how Parkinson's disease emerges and progresses, and current treatments have limited effects," says Manzanares, who hopes these analyses will help design more effective, personalized therapies in the future.

The exploratory study included 23 patients with Parkinsonism and 16 healthy controls. Despite the small sample size, the findings are consistent with other independent studies conducted in Italy and the United States over the past decade, confirming the diagnostic potential of this approach.

The research team includes Francisco Navarrete, Marina Guillot, Lorena Martínez, Daniela Navarro, José A. Molina, José P. López-Atalaya, and Jorge Manzanares (UMH-CSIC, RIAPAd, ISABIAL, and Hospital 12 de Octubre).

The project was supported by ICAR Foundation, ISABIAL, the Ministry of Education, Vocational Training and Sports, the Tatiana Pérez de Guzmán el Bueno Foundation, the Spanish State Research Agency, the Generalitat Valenciana (Prometeo Program), and the Ministry of Science, Innovation and Universities.