Affective and chronic fatigue symptoms are associated with serum neuronal damage markers in Parkinson’s disease

Parkinson's disease (PD) is frequently accompanied by mood and chronic fatigue syndrome (CFS) symptoms. The aim of this study is to examine whether the affective and CFS symptoms due to PD are associated with serum biomarkers of neuronal injury in association with immune activation and insulin resistance. Using a case (70 PD patients) control (60 healthy controls) study design, we assessed affective and CFS symptoms, measured the peripheral immune-inflammatory response system (IRS) using interleukin-6 (IL-6), IL-10, zinc, and calcium levels, the Homeostasis Model Assessment 2 insulin resistance (HOMA2IR) index, and serum brain injury markers including S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), phosphorylated tau217 (pTau217), and glial fibrillary acidic protein (GFAP). The aim is to examine whether immune, IR, and/or brain injury biomarkers determine affective and CFS symptoms due to PD. PD patients showed increased affective and CFS scores, IRS activation, HOMA2IR, NSE, GFAP, pTau217, and S100B levels as compared to controls. A large part (52.5%) of the variance in the mood + CFS score was explained by the regression on NSE, S100B, HOMA2IR index, IL-10 (all positively), and calcium (inversely). The HOMA2IR and IRS indices were significantly associated with all 4 brain injury biomarkers. A large part of the variance in the latter markers (37.0%) was explained by the cumulative effects of the IRS and HOMA2IR indices. IRS activation and IR in patients with PD contribute to damage to glial cell projections and type III intermediate filament, which in turn contribute to affective and CFS symptoms.