Stable isotope dilution ultra-high performance liquid chromatography-tandem mass spectrometry quantitative profiling of tryptophan-related neuroactive substances in human serum and cerebrospinal fluid.

Many compounds related to L-tryptophan (L-TRP) have interesting biological or pharmacological activity, and their abnormal neurotransmission seems to be linked to a wide range of neurodegenerative and psychiatric diseases. A high-throughput method based on ultra-high performance liquid chromatography connected to electrospray tandem mass spectrometry (UHPLC-ESI-MS/MS) was developed for the quantitative analysis of L-TRP and 16 of its metabolites in human serum and cerebrospinal fluid (CSF), representing both major and minor routes of L-TRP catabolism. The combination of a fast LC gradient with selective tandem mass spectrometry enabled accurate analysis of almost 100 samples in 24h. The standard isotope dilution method was used for quantitative determination. The method's lower limits of quantification for serum and cerebrospinal fluid ranged from 0.05 to 15nmol/L and 0.3 to 45nmol/L, respectively. Analytical recoveries ranged from 10.4 to 218.1% for serum and 22.1 to 370.0% for CSF. The method's accuracy ranged from 82.4 to 128.5% for serum matrix and 90.7 to 127.7% for CSF matrix. All intra- and inter-day coefficients of variation were below 15%. These results demonstrate that the new method is capable of quantifying endogenous serum and CSF levels of a heterogeneous group of compounds spanning a wide range of concentrations. The method was used to determine the physiological levels of target analytes in serum and CSF samples from 18 individuals, demonstrating its reliability and potential usefulness in large-scale epidemiological studies.

Tau protein, beta-amyloid1₋42 and clusterin CSF levels in the differential diagnosis of Parkinsonian syndrome with dementia.

BACKGROUND: Parkinson's disease (PD), PD with dementia (PDD) and Lewy body dementia (DLB) are synucleinopathies. PDD and DLB are sometimes considered a transition between PD and Alzheimer dementia (AD). Finding in vivo markers or their combination could help in the differential diagnosis of these neurodegenerative (ND) diseases. OBJECTIVE: The aim of this study was to assess cerebrospinal fluid (CSF) levels of tau protein, betaamyloid1-42 and clusterin and to compare these levels among patients with probable PD, PDD, DLB and AD. METHODS: CSF levels of ND markers were assessed in 96 patients (27 patients with PD, 14 with PDD, 14 with DLB, 17 with AD and 24 subjects as a control group). RESULTS: In all of the groups of patients, beta-amyloid1-42 levels were decreasing in the order PD>PDD>DLB>AD, whereas tau protein and the tau protein/beta-amyloid1-42 index were increasing in the same order (PD

Cerebrospinal fluid levels of chromogranin A in the treatment-naïve early stage Parkinson's disease: a pilot study.

Chromogranin A (CgA) levels in cerebrospinal fluid (CSF) have been reported to be significantly reduced in the later stages of Parkinson's disease (PD). There are only limited data regarding its levels in the early stages, so its significance as a potential biomarker in the diagnosis of PD cannot be established. The aim of our study was to establish the level of CgA in a cohort of treatment-naïve patients with early stage PD. Ten patients (4 males, 6 females) and 10 gender- and age-matched controls were examined for CgA levels in the CSF. Control subjects were patients with low-back pain or tension-type headache. The mean CSF CgA level in PD patients was 74.8 (41.9-123.8) µg/l; in the control group it was 143.9 (116-181.3) µg/l. Statistical analysis showed a difference at the significance level P ≤ 0.05. Our pilot study shows that CSF CgA levels are reduced in the early stages of PD. CgA could therefore be a potential biomarker helpful in the diagnosis of PD.