Biofluids profile of α-Klotho in patients with Parkinson's disease.

We measured α-Klotho in CSF and serum of PD patients at early stage of the disease, finding two distinct pools, the first increased, the second reduced. CSF α-Klotho was inversely associated with CSF α-synuclein levels. Our preliminary results suggest α-Klotho as potential biomarker or therapeutic target in PD.

Amyloid-ß42/Neurogranin Ratio as a Potential Index for Cognitive Impairment in Parkinson's Disease.

BACKGROUND: Synaptopathy is critical in pathophysiology of Parkinson's disease (PD). Cerebrospinal fluid (CSF) levels of neurogranin (NG) and amyloid-ß42 (Aß42) are considered markers of synaptic dysfunction in neurodegenerative diseases. OBJECTIVE: To evaluate the CSF synaptopathy-related biomarkers, especially the novel Aß42/NG ratio, in PD, establishing possible associations with cognitive level and other clinical parameters. METHODS: Levels of NG, Aß42, amyloid-ß40, total and phosphorylated tau, and Aß42/NG ratio were measured in 30 PD patients and 30 controls and correlated with cognitive and motor parameters. The accuracy in distinguishing the cognitive status was determined. RESULTS: NG and Aß42 were significantly reduced in PD, with higher NG levels in patients with worse cognition. The Aß42/NG ratio showed a direct correlation with Mini-Mental State Examination, independently from age and sex, and differentiated cognitively impaired patients with 92% sensitivity and 71.4% specificity, accuracy higher than NG alone. No correlations resulted with motor disturbances or therapy. CONCLUSIONS: The novel Aß42/NG ratio couples either presynaptic or postsynaptic markers of synaptic dysfunction, representing a potential global index of synaptopathy, useful to track cognitive functions in PD.

CSF α-synuclein inversely correlates with non-motor symptoms in a cohort of PD patients.

INTRODUCTION: Although non-motor symptoms are early and disabling features of PD, reliable predictors and effective therapies are not yet available. Measurement of CSF proteins mirroring brain pathology is currently utilized for diagnostic and prognostic clustering of patients with neurodegenerative diseases but the association with non-motor symptoms in PD has not been evaluated. Here we performed a cross-sectional correlation study, aimed at identifying potential fluid biomarkers for non-motor symptoms in PD. METHODS: CSF levels of 42-amyloid-ß, total and phosphorylated tau, α-synuclein and reciprocal ratios were measured in a group of 46 PD patients compared to 37 gender/age-matched controls and correlated with standard clinical scores for motor and non-motor features. RESULTS: We observed that α-synuclein levels were reduced in PD (p < 0.05, AUC = 0.8; p < 0.05) and inversely correlated with non-motor symptoms scale total score and items 3 and 9, even independently from age, disease duration, motor impairment severity and dopaminergic treatment (T = -2,9, p < 0.014; T = -3.6, p < 0.05; item 9: T = -2.1, p < 0.05, respectively). CONCLUSIONS: Our findings suggest that the reduction of CSF α-synuclein may parallel degeneration of non-dopaminergic systems. Although confirmatory studies are necessary, CSF α-synuclein reduction might represent a potential biomarker to monitor non-motor symptoms burden.