A research team from Baylor College of Medicine and the Duncan Neurological Research Institute at Texas Children’s Hospital has identified a sequence of biological events that links genetic changes to disruptions in lipid metabolism, which may contribute to the development of Parkinson’s disease. The study, published in Brain, suggests potential avenues for early diagnosis and intervention before symptoms arise.
“Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer's disease, affecting more than 10 million people worldwide. We know more than 100 genes that increase the risk of developing the disease but, in most cases, we do not understand how the genetic change leads to the condition,” said corresponding author Dr. Joshua Shulman, professor at Baylor College of Medicine and co-director of the Duncan NRI.
The research focused on a common gene variant called SPTSSB (rs1450522), which plays a role in sphingolipid synthesis. This variant has been associated with a modest increase in Parkinson’s risk. By studying blood samples from healthy individuals carrying this variant, researchers found increased production of SPTSSB protein in neurons and higher levels of sphingolipids compared to those without the variant. “We found that this risk variant increases the amount of protein SPTSSB produced in the brain, especially in neurons, and the levels of sphingolipids in blood, when compared to individuals not carrying this variant. Out of 62 sphingolipids that we measured, 23% were significantly altered,” Shulman explained.
Further analysis involved comparing metabolites in blood samples from 149 people with Parkinson’s and 150 without. “We identified multiple other lipids that were altered in patients with Parkinson’s disease. For instance, fatty acids were present at lower levels in patients than in people without the condition. Interestingly, healthy individuals carrying the SPTSSB variant who had higher levels of multiple sphingolipids in blood also had lower levels of certain fatty acids,” Shulman said.
The findings were validated using data from thousands more individuals. Statistical modeling showed that rs1450522 is linked to increased Parkinson’s risk through its effect on lipid metabolism. According to Shulman: “we think they are important primarily because they give us insights into a mechanism, a process that triggers and sustains the condition. Understanding how these lipid metabolic changes set the path to Parkinson’s disease can guide the development of treatments to prevent or delay the onset of symptoms.”
The team aims to develop early diagnostic markers detectable by blood tests based on these findings. “Currently, early diagnosis remains an unsolved challenge in Parkinson’s research,” Shulman noted. “We need sensitive, specific tests that can detect the disease before symptoms appear. By the time patients come to see me because of their symptoms, often their brains are already significantly affected, and we can only treat the symptoms for which we have effective therapies. But we still lack options for early diagnosis or for delaying or preventing this devastating disease.”
Baylor College of Medicine operates as an independent health sciences university advancing research, education across its schools—including medicine and biomedical sciences—and patient care through clinical partnerships (https://www.bcm.edu/news). Community service is among its core missions (https://www.bcm.edu/news), and it collaborates within integrated health science environments (https://www.bcm.edu/news). Paul Klotman serves as president and chief executive officer (https://www.bcm.edu/news). Founded in 1900 and relocated to Houston's Texas Medical Center in 1943, Baylor continues supporting education initiatives while promoting research partnerships (https://www.bcm.edu/news).
For additional details about contributors and funding sources for this work, refer to the original publication.
