Parkinson’s disease is a complex neurodegenerative disorder. The causes are still unclear, but about 10% to 15% of cases are thought to be due to genetic changes, while exposure to certain things in the environment, such as pesticides and dry cleaning chemicals, have also been linked to the disorder. Now scientists have revealed more about a chain of molecular events that likely occur in Parkinson’s patients. These findings, which were reported in Brain, may help scientists create better methods doe early diagnosis and treatment.
Parkinson's disease is estimated to impact over 10 million people around the world. Although about changes have been found in over 100 genes that can influence the risk of getting Parkinson’s, there is still a lot we do not know about how genetic alterations may cause the disease, noted corresponding study author Dr. Joshua Shulman, a professor at Baylor College of Medicine, among other appointments.
Some genes that have been linked to Parkinson’s development are related to lipid metabolism. One risk gene called SPTSSB, for example, is related to the production of molecules known as sphingolipids. A small change or variation in this gene called rs1450522 has previously been linked to a small increase in the risk of Parkinson's.
The researchers looked for relevant biomarkers by analyzing metabolites in 149 Parksinon’s patients, and comparing them to 150 unaffected individuals’ metabolites.
"We studied blood samples of people carrying this genetic variant who were healthy—they did not show any symptoms of the condition, like tremors, limb stiffness, gait and balance problems," Shulman said. "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."
The researchers also found changes in other lipids in patients with Parkinson's disease, too. "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 their blood also had lower levels of certain fatty acids," Shulman said.
The results were confirmed using datasets that contained health data from thousands of people.
The rs1450522 variant of SPTSSB was confirmed to raise Parkinson's risk, and lead to higher SPTSSB protein levels, which also changed lipid metabolism. These change may actually cause Parkinson’s disease, although more research will be needed to confirm that hypothesis.
These genetic changes cause only a small change in lipids, but Shulman noted that they may still reveal “a process that triggers and sustains the condition.” And, if we can fully understand these events, scientists can develop better treatments or even preventive strategies. The findings could also lead to the development biomarkers that could be used in a blood test for Parkinson’s.
"Currently, early diagnosis remains an unsolved challenge in Parkinson's research," noted Shulman. "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."
Sources: Baylor College of Medicine, Brain