Alpha-synuclein — the protein that clumps in the cells of Parkinson’s patients — is currently the major focus of Parkinson’s biomarker studies. Researchers are analyzing biosamples (spinal fluid, blood, tissue) to make a connection between alpha-synuclein and risk, onset or progression of Parkinson’s disease (PD). The latest findings, published in The American Journal of Pathology, report that patients with higher levels in spinal fluid experienced faster cognitive decline.

In a project funded by The Michael J. Fox Foundation (MJFF), Jing Zhang, MD, PhD, and his team at the University of Washington in Seattle examined samples and data from PD patients obtained in the DATATOP study. Led by the Parkinson’s Study Group in the late 1980s, the deprenyl and tocopherol antioxidative therapy of parkinsonism (DATATOP) study collected samples and clinical data from PD subjects for up to eight years.

In this latest analysis, researchers compared alpha-synuclein levels to scores from tests of cognition, such as verbal learning and memory, visuospatial memory and processing speed, among 304 PD patients. They found that patients with higher levels of alpha-synuclein in spinal fluid had faster cognitive decline.

“This is a surprising conclusion,” says Mark Frasier, PhD, MJFF vice president of research programs. “One would think that people with more cognitive problems would have less alpha-synuclein in spinal fluid because more would be caught up in the brain causing those problems.”

Zhang’s group also reported that while alpha-synuclein levels decreased significantly over two years, that decline could not predict motor symptoms. These findings join a list of observations about how alpha-synuclein in spinal fluid relates to PD. Initial analysis from the MJFF-sponsored Parkinson’s Progression Markers Initiative (PPMI) reported last year that PD patients had lower alpha-synuclein levels in spinal fluid compared to controls. They also found that patients with posture/gait disturbance averaged lower alpha-synuclein than patients with tremor-dominant PD.

Further investigation into alpha-synuclein continues in PPMI and other studies. Zhang and his coauthors cited PPMI as a potential source for validation of their cognition findings. Since PPMI includes healthy controls, researchers could test whether those results are PD-specific or seen in healthy aging adults with cognitive decline, too.

To accelerate research around PD biomarkers, MJFF spearheaded an effort to make data and samples from varied Parkinson’s studies available to investigators. The Foundation also offers funding to use the data and samples, such as to Zhang for the DATATOP analysis.