Neurofilament Light Chain (NfL) Levels are Increased After Sleep in Parkinson Disease (PD)
Caileigh Dintino1, Theresa Swift-Scanlan2, Unsong Oh1, Elizabeth Crump1, Erika Shelton3, Samantha Holden4, Josiane Broussard5, Matthew Barrett1, Nitai Mukhopadhyay6, Sarah Lageman1, Brian Berman1
1Virginia Commonwealth University Department of Neurology, 2Virginia Commonwealth University School of Nursing, 3University of Colorado, 4University of Colorado School of Medicine, 5Colorado State University, 6Virginia Commonwealth University Department of Biostatistics
Objective:
Evaluate if sleep in PD is associated with changes in blood-based biomarker levels.
Background:
Sleep disturbances in PD can contribute to disease progression and increase risk of dementia.1-7 An impaired glymphatic system, which functions mainly during sleep and removes soluble proteins and metabolites from the central nervous system, has been linked to neurodegeneration.8 Whether disrupted sleep in PD is associated with changes in the levels of neuroinflammatory and neurodegenerative biomarkers used to study disease progression and cognitive decline, is not known.
Design/Methods:
Non-demented PD patients aged 50-80 underwent an overnight polysomnogram with blood drawn at 8:00pm (PM) and 6:30am (AM). Plasma samples were analyzed using Meso Scale Discovery immunoassays for neuroinflammatory biomarkers interleukin6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor alpha (TNF-a), and the U-PLEX assay for alpha-synuclein. Neurofilament light chain (NfL), which is released from axons upon injury or neuronal death,9 was measured using Quanterix Simoa Assays. T-tests were used to compare overnight changes in biomarker levels, and correlations were tested with Pearson coefficients. Significance threshold was p<0.05.
Results:
31 PD patients (18M:13F, 67.4±6.0 yrs) were enrolled: 23 with normal cognition (PD-NC; 11M:12F, 67.4 ±6.0 yrs) and 8 with mild cognitive impairment (PD-MCI; 7M:1F, 68.4 ±6.6 yrs). Morning NfL levels were 16.5% higher in PD-MCI (PM: 13.70 ±4.15, AM: 16.38 ±7.79; p=0.043), but not significantly different in PD-NC (PM: 17.24 ±7.88, AM: 18.82 ±7.93; p=0.091). Morning levels of TNF-a were also higher in PD-MCI (PM: 1.83 ±0.88, AM: 1.86 ±0.87; p=0.02), but not in PD-NC (PM: 1.65 ±0.54, AM: 1.71 ±0.5; p=0.38). No significant change in levels were found for IL-6, MCP-1, or alpha-synuclein.
Conclusions:
Plasma levels of NfL and TNF-a can be altered by sleep in PD-MCI patients. Sleep-related mechanisms of cerebrospinal fluid clearance may need to be considered in the application of NfL as a PD biomarker.