Whitley W Aamodt1, Teresa Waligorska2, Junchao Shen1,3, Thomas F Tropea1,3, Andrew Siderowf1,3, Daniel Weintraub3,4,5, Murray Grossman1,3, David Irwin1,3, David A Wolk1, Sharon X Xie6, John Q Trojanowski2,3, Leslie M Shaw2,3, Alice S Chen-Plotkin1,3. 1. Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 2. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 3. Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 4. Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 5. Parkinson's Disease and Mental Illness Research, Education, and Clinical Centers, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA. 6. Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Abstract
BACKGROUND: Neurofilament light chain protein (NfL) is a promising biomarker of neurodegeneration. OBJECTIVES: To determine whether plasma and CSF NfL (1) associate with motor or cognitive status in Parkinson's disease (PD) and (2) predict future motor or cognitive decline in PD. METHODS: Six hundred and fifteen participants with neurodegenerative diseases, including 152 PD and 200 healthy control participants, provided a plasma and/or cerebrospinal fluid (CSF) NfL sample. Diagnostic groups were compared using the Kruskal-Wallis rank test. Within PD, cross-sectional associations between NfL and Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) and Mattis Dementia Rating Scale (DRS-2) scores were assessed by linear regression; longitudinal analyses were performed using linear mixed-effects models and Cox regression. RESULTS: Plasma and CSF NfL levels correlated substantially (Spearman r = 0.64, P < 0.001); NfL was highest in neurocognitive disorders. PD participants with high plasma NfL were more likely to develop incident cognitive impairment (HR 5.34, P = 0.005). CONCLUSIONS: Plasma NfL is a useful prognostic biomarker for PD, predicting clinical conversion to mild cognitive impairment or dementia.
BACKGROUND: Neurofilament light chain protein (NfL) is a promising biomarker of neurodegeneration. OBJECTIVES: To determine whether plasma and CSF NfL (1) associate with motor or cognitive status in Parkinson's disease (PD) and (2) predict future motor or cognitive decline in PD. METHODS: Six hundred and fifteen participants with neurodegenerative diseases, including 152 PD and 200 healthy control participants, provided a plasma and/or cerebrospinal fluid (CSF) NfL sample. Diagnostic groups were compared using the Kruskal-Wallis rank test. Within PD, cross-sectional associations between NfL and Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) and Mattis Dementia Rating Scale (DRS-2) scores were assessed by linear regression; longitudinal analyses were performed using linear mixed-effects models and Cox regression. RESULTS: Plasma and CSF NfL levels correlated substantially (Spearman r = 0.64, P < 0.001); NfL was highest in neurocognitive disorders. PD participants with high plasma NfL were more likely to develop incident cognitive impairment (HR 5.34, P = 0.005). CONCLUSIONS: Plasma NfL is a useful prognostic biomarker for PD, predicting clinical conversion to mild cognitive impairment or dementia.
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