Intrathecal IgG synthesis in patients with alterations in the neurochemical dementia diagnostics.

Neurochemical Dementia Diagnostics (NDD), i.e., analysis of the cerebrospinal fluid (CSF) concentrations of amyloid-beta peptides and tau/phospho-tau proteins plays important role in the diagnosis of neurodegeneration and dementias. Several studies show alterations of these biomarkers in Alzheimer's disease (AD), however, only a few reports address alterations of other CSF biomarkers (albumin and immunoglobulins' quotients, cell count, lactate concentration, etc.) in the pathophysiology and diagnostic procedures of dementias. Therefore, we analyzed these biomarkers in patients diagnosed for dementia syndromes and carefully characterized with the state-of-the-art NDD analysis: Abeta1-42, Abetax-42, Abetax-42/x-40 ratio, tau, and ptau181. We found intrathecal IgG synthesis in 5 out of 112 patients showing alterations of the NDD biomarkers, and in four out of these five subjects, we could not find any satisfying reason for the intrathecal humoral response. In 25.9% of the patients with altered NDD biomarkers, we found an increased albumin quotient indicating a dysfunction of the blood-CSF barrier; however a similar figure of 25.2% was found in the group of patients without alterations in the NDD. Our findings suggest that at least some patients with increased CSF concentrations of tau/ptau proteins and decreased concentrations of Abeta{42} peptides show simultaneously CSF alterations found otherwise in neuroinflammatory processes. This, in turn, suggests that extended diagnosis should be performed in patients with "isolated" alterations of NDD biomarkers or intrathecal immunoglobulin synthesis.

Decreased serum activity of semicarbazide-sensitive amine oxidase (SSAO) in patients treated with second generation antipsychotics: a link to impaired glucose metabolism?

OBJECTIVE: Although the treatment of schizophrenia with many second generation antipsychotics is known to be associated with metabolic changes, such as hyperglycemia or hypercholesterolemia, the underlying mechanisms of these adverse reactions remain unclear. In light of the recent focus on the involvement of semicarbazide-sensitive amine oxidase (SSAO) in glucose metabolism, we investigated SSAO serum activity in schizophrenic patients treated with antipsychotics with the objective of determining a possible link between SSAO and impaired glucose metabolism. METHODS: Blood samples were drawn from 44 schizophrenic patients (24 receiving second generation antipsychotics known to disturb glucose metabolism) on day 1 and day 5 of inpatient treatment. Forty-one healthy adults with no medical condition known to influence SSAO served as controls. RESULTS: Of the 44 schizophrenic patients, the 24 treated with second generation antipsychotics known to disturb glucose metabolism showed significantly lower SSAO serum activity [day 1 (mean +/- SD): 477 +/- 105 mU/L; day 5: 438 +/- 86 mU/L] than the 20 patients treated with other antipsychotics not known to influence glucose metabolism (day 1: 513 +/- 124 mU/L, p = 0.359; day 5: 542 +/- 204 mU/L, p = 0.021) only after 5 days of treatment and compared to healthy controls (526 +/- 142 mU/L, p = 0.021). No differences were observed between schizophrenic patients treated with first generation antipsychotics and the controls. CONCLUSION: We found decreased SSAO serum activity exclusively in schizophrenic patients treated with second generation antipsychotics known to disturb glucose metabolism. In terms of the role of SSAO in glucose metabolism, the observed decrease in SSAO serum activity may be linked to metabolic changes that are known to occur in schizophrenic patients being treated with many second generation antipsychotics.

International quality control survey of neurochemical dementia diagnostics.

UNLABELLED: Currently, neurochemical dementia diagnostics (NDD) are increasingly entering routine clinical neurochemistry, offering improved early and differential diagnosis of dementias. However, there is an obvious lack of standardization in pre-analytical sample handling and systematic quality surveys. Therefore, in this study, 14 laboratories in Germany, Austria, and Switzerland were given aliquots of a human cerebrospinal fluid (CSF) sample, and were asked to measure Alzheimer's disease (AD) biomarkers (amyloid beta (Abeta) peptides, total Tau protein, and phosphorylated Tau protein (P-tau(181P))) according to their routine protocols. RESULTS: The inter-laboratory coefficients of variation of the results obtained by the laboratories participating in this study were in the range of 20-30%. Although the results of this quality control survey are promising, the quality of measurements has to be further optimized.

Decreased serum semicarbazide sensitive aminooxidase (SSAO) activity in patients with major depression.

Semicarbazide sensitive aminooxidase (SSAO) is known to interplay with monoamine oxidases (MAO) and several antidepressants. Taking into account the monoamine hypothesis concerning the pathophysiology of depression, the aim of the present pilot study was to evaluate serum SSAO activity in depressed patients. A total of 21 inpatients with major depression and 41 healthy controls were studied. Serum SSAO activity was determined by HPLC on days 1, 5 and 10 of inpatient treatment. At baseline without medication including antidepressants, highly depressed patients (MADRS score>or=30) had significantly decreased serum SSAO activity (mean 385+/-161 mU/l) when compared to healthy controls (mean 526+/-141 mU/l; p=0.003). This SSAO decrease was less pronounced at day 5 and day 10 under an antidepressive drug regime. Decreased serum SSAO activity was observed in patients with major depression, especially in those with high MADRS scores. The present results support the hypothesis of dysfunctional monoaminergic metabolism in the pathogenesis of depressive disorders. The disputable association between depression and monoamine metabolism requires further investigation, particularly with regard to SSAO activity and medication status.

Serum level of semicarbazide-sensitive amine oxidase in children with ADHD.

BACKGROUND: The objective of this study was to analyze the extracellularly acting semicarbazide-sensitive amine oxidase (SSAO) serum levels in children with ADHD for the first time. SSAO is known to show deviations from normal in various somatic disorders and to interplay with the intracellularly active MAO. In humans two forms of SSAO a circulating form in plasma and a membrane-bound form are involved in monoaminergic metabolism. METHODS: We analyzed serum levels of SSAO in 27 children meeting ICD-10 criteria of Hyperkinetic Disorder (F90) or DSM-IV criteria of ADHD combined type by HPLC method and fluorimetric detection. A group of 42 healthy volunteers within the same age range (7.0 - 14.0 years) served as controls. RESULTS: No significant differences between children with ADHD (SSAO activity M = 773, SD = 217 mU/l) and healthy controls (SSAO activity M = 775, SD = 256 mU/l) in SSAO serum levels were found (F = 2.18; p > 0.14). Further, stimulant medication status had no influence on the result (F = 2.52; p > 0.11). CONCLUSION: There is no evidence for a deviation of SSAO serum activity in ADHD. Hence, extracellularly acting SSAO does not seem to be a promising factor for further research in ADHD. But progress in knowledge of its physiologic role and of the relationship between the membrane-bound and the circulating serum form may open new avenues for research on SSAO in ADHD.

Elevated homocysteine levels in aqueous humor of patients with pseudoexfoliation glaucoma.

PURPOSE: To determine total homocysteine levels in aqueous humor of pseudoexfoliation open-angle glaucoma patients. DESIGN: Case-control study. METHODS: Total homocysteine levels were measured by enzyme-linked immunosorbent assay in aqueous humor and plasma of 29 patients with pseudoexfoliation glaucoma and 31 control patients with cataract. Patients with factors affecting homocysteine levels were excluded. RESULTS: We observed significantly elevated (twofold) homocysteine levels in the aqueous humor of the glaucoma patients (Z = -5.11, P <.0001). Additionally, the calculated ratio (plasma:aqueous humor) was significantly lower in these patients (Z = -3.57, P <.001), and aqueous homocysteine was significantly correlated with their respective elevated plasma levels (r =.42, P =.02). CONCLUSIONS: Because homocysteine induces vascular injury and alterations of extracellular matrix, high aqueous homocysteine may trigger the abnormal matrix accumulation characteristic. It may reflect the proposed impairment of the blood-aqueous barrier of pseudoexfoliation open-angle glaucoma and be involved in its pathogenesis.

Tau protein phosphorylated at threonine 181 in CSF as a neurochemical biomarker in Alzheimer's disease: original data and review of the literature.

Cerebrospinal fluid (CSF) concentrations of total Tau and Tau phosphorylated at threonine (position 181 [pTau181]) were studied with ELISA in a group of carefully selected patients with a neurochemically supported diagnosis of Alzheimer's disease (AD, n = 9; age range, 51-89 yr) and in a group of sex- and age-matched nondemented controls (n = 9; age range, 52-81 yr). The concentration of both biomarkers is increased significantly in the AD group (total Tau, p < 0.0008; pTau181, p < 0.008). A significant correlation between CSF concentrations of both biomarkers is observed (R = 0.897; p < 0.001). Neither total Tau nor pTau181 correlates with age or degree of memory impairment, and only a tendency is observed between the concentrations of total Tau and Abeta42 in the CSF. Our results further confirm a possible role of pTau181 as a diagnostic tool in AD. The current literature regarding the physiological and pathological role of phosphorylated Tau proteins is reviewed, as well as the role of these proteins as promising biomarkers in the diagnosis of neurodegenerative disorders.