Lower levels of two proteins in the spinal fluid of Parkinson’s disease patients were found to be related to specific symptoms, suggesting they could be used as biomarkers for the disease, according to an observational study.
Parkinson’s patients with postural instability and gait difficulty were found to have significantly lower levels of the protein alpha-synuclein in their cerebrospinal fluid. Alpha-synuclein has been linked to protein clumps in the brain that are the hallmarks of Parkinson’s. In addition to the brain, the protein is also found in peripheral tissues and body fluids.
Levels of the protein beta-amyloid — commonly associated with Alzheimer’s disease — were also lower than normal, and related to cognitive impairment in patients with moderate to advanced Parkinson’s disease.
“These associations between protein levels and clinical symptoms can help us select participants for clinical trials. For example, people with lower beta-amyloid may be more likely to develop memory problems and therefore would benefit more from a cognitive therapy,” said Jennifer G. Goldman, MD, MS, associate professor at Rush University Medical Center in Chicago and first author of the study. “Enrolling this population in trials can help us see a treatment effect more clearly than testing the therapy on people who will not have this symptom.”
The study, “Cerebrospinal fluid, plasma, and saliva in the BioFIND study: Relationships among biomarkers and Parkinson’s disease Features, was published in the journal Movement Disorders.
Called BioFIND (NCT01705327), the cross-sectional study is a pioneering effort to differentiate biomarkers of neurodegeneration in Parkinson’s disease based on fluids collected from patients’ spinal fluid, blood, and saliva. Sponsored by the Michael J. Fox Foundation, with support from the National Institute of Neurological Disorders and Stroke and the National Institutes of Health, it aims to ultimately improve diagnosis and treatment of patients with this disease.
Data and body fluid samples were collected from 126 patients with moderately advanced Parkinson’s disease and 106 healthy volunteers from eight clinical sites in the United States.
Led by Un Jung Kang, MD, chief of the division of movement disorders at Columbia University in New York, researchers profiled Parkinson’s-associated protein levels in these biofluids and their relationships to clinical features of the disease.
The study found that while alpha-synuclein levels in cerebrospinal fluid from Parkinson’s patients with certain motor function impairments — specifically balance and walking issues — were lower compared with healthy volunteers, they did not differ when measured in saliva or plasma samples. This correlation was not found for all other proteins analyzed, suggesting that cerebrospinal fluid alpha-synuclein is a specific biomarker for these motor symptoms.
Beta-amyloid protein levels were also lower in cerebrospinal fluid samples of Parkinson’s patients than healthy controls. Only cerebrospinal fluid beta-amyloid was found to correlate with cognitive response in these patients as measured by a cognitive recall test.
“This report is an important contribution in our efforts to understand and quantify Parkinson’s biology to accelerate drug development,” Mark Frasier, PhD, senior vice president of research programs at The Michael J. Fox Foundation for Parkinson’s Research (MJFF), and co-author of the study, said in a press release. “BioFIND is a partnership between our Foundation, academia, government and — most importantly — research volunteers to measure this disease and the impact of new treatments.”
Additional studies in large patient groups are necessary to further validate these findings. The team is planning to evaluate these potential cerebrospinal fluid biomarkers in the Parkinson’s Progression Markers Initiative, an MJFF-sponsored study following more than 1,500 people with Parkinson’s or who are at risk of developing the disease, as well as control volunteers, for more than five years.