Objective: To evaluate cerebrospinal fluid (CSF) levels of proteins associated with neuropathological inclusions and their ratios, and CSF and plasma levels of inflammatory proteins as potential biomarkers for mild cognitive impairment in PD (PD-MCI). Parkinson’s Progression Markers Initiative (PPMI) dataset was used as a replication cohort.

Background: No CSF or plasma biomarker has been validated for the diagnosis of PD-MCI or PD associated dementia (PDD).

Methods: CSF levels of α-synuclein, amyloid-ß1-42 (Aß1-42), total tau (T-Tau) and thr-181 phosphorilated tau (P-Tau), as well as CSF and plasmatic levels of cytokines (IL-1ß, IL-2, IL-6, IFNγ, and TNF-α) were studied in 40 non-demented PD patients (25 PD-MCI and 15 cognitively normal (PDCN)). Plasmatic cytokines were measured in 50 patients (29 PD-MCI and 21 PDCN). PD-MCI was diagnosed according to MDS Task Force (level II) (1). The PPMI dataset was explored for baseline predictors of dementia and decline in specific domains at 3-year follow-up.

Results: There were no differences between PD-MCI and PDCN patients in any of the CSF and plasmatic proteins or in their ratios. T-Tau/Aß1-42 (r=-0.450; p= 0.018) and T-Tau/Aß1-42+α-synuclein (r=-0.501; p=0.007) ratios negatively correlated with memory z score. T-Tau/α-synuclein (r=-0.490; p=0.003) and P-Tau/α-synuclein (r=-0.347; p=0.007) negatively correlated with score of intersecting pentagons. T-Tau/α-synuclein ratio negatively correlated with score of MOCA (r=-0.432; p= p=0.030). Plasmatic IL-6 levels negatively correlated with MOCA score (r=-0.429; p=0.024) and language z score (r=-0.553; p=0.002). PPMI cohort: baseline T-Tau/Aß1-42 (p=0.001), T-Tau/α-synuclein (p=0.001), and T-Tau/Aß+α-synuclein (p<0.001) ratios were higher in PD that progressed to dementia. In addition, T-Tau/Aß1-42, T-Tau/α-synuclein, and T-Tau/Aß1-42+α-synuclein ratios were independent predictors of decline in MOCA and T-Tau/Aß1-42 of decline in memory z score.

Conclusions: T-Tau/Aß1-42, T-Tau/α-synuclein and T-Tau/α-synuclein+Aß1-42 may have a value as predictors of dementia in PD. They might be useful to diagnose PD-MCI patients at high risk of dementia and to identify subtypes of evolution, as ratios with Aß1-42 are more related with memory decline whereas those with α-synuclein are associated with visuospatial decay. Plasmatic IL-6 might also be useful as biomarker of progression of cognitive impairment in PD.

References: 1. Litvan I, Goldman JG, Troster AI, et al. Diagnostic criteria for mild cognitive impairment in Parkinson’s disease: Movement Disorder Society Task Force guidelines. Mov Disord. Mar 2012;27(3):349-356.

« Back to 2017 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/the-value-of-classical-cerebrospinal-fluid-protein-ratios-and-peripheral-inflammation-in-parkinsons-disease-cognitive-impairment/