Serum heart-type fatty acid-binding protein and cerebrospinal fluid tau: Marker candidates for dementia with Lewy bodies

Background: The measurement of biomarkers in cerebrospinal fluid (CSF) has gained increasing acceptance in establishing the diagnosis of some neurodegenerative diseases. Heart-type fatty acid-binding protein (H-FABP) was recently discovered in CSF and serum of patients with neurodegenerative diseases. Objective: We investigated H-FABP in CSF and serum alone and in combination with CSF tau protein to evaluate these as potential biomarkers for the differentiation between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Methods: We established H-FABP and tau protein values in a set of 144 persons with DLB (n = 33), Parkinson disease with dementia (PDD; n = 25), AD (n = 35) and nonclemented neurological controls (NNC; n = 51). Additionally, serum H-FABP levels were analyzed in idiopathic Parkinson disease patients without evidence of cognitive decline (n = 45) using commercially available enzyme-linked immunosorbent assays. We calculated absolute values of HFABP and tau protein in CSF and serum and established relative ratios between the two to obtain the best possible match for the clinical working diagnosis. Results: Serum HFABP levels were elevated in DLB and PDD patients compared with NNC and AD subjects. To better discriminate between DLB and AD, we calculated the ratio of serum H-FABP to CSF tau protein levels. At the arbitrary chosen cutoff ratio >= 8 this quotient reached a sensitivity of 91% and a specificity of 66%. Conclusion: Our results suggest that the measurement of CSF tau protein, together with H-FABP quantification in serum and CSF, and the ratio of serum H-FABP to CSF tau protein represent marker candidates for the differentiation between AD and DLB. Copyright (c) 2007 S. Karger AG, Basel

Современное состояние и перспективы развития ООПТ Томской области

В работе дана характеристика сети особо охраняемых природных территорий Томской области, ее роли в поддержании эколого-хозяйственного баланса области. Определены этапы формирования сети ООПТ. Дан анализ географического разнообразия сети ООПТ и представленности ее в административных районах области. Определена роль сети ООПТ в сохранении редких и исчезающих видов растений и животных. Разработана и реализована методика комплексной оценки эффективности сети ООПТ. Предложены пути ее развития и оптимизации.In work the characteristic of the network of specially protected natural territories of the Tomsk region, its role in maintaining ecological and economic balance of the region. The stages of forming a network of protected areas. The analysis of the geographic diversity of the PA network and its representation in the administrative districts of the region. Defined the role of the network of protected areas in the conservation of rare and endangered species of plants and animals. Developed and implemented a methodology of comprehensive evaluation of the effectiveness of the PA network. The proposed ways of its development and optimization

Проектирование системы электроснабжения электротехнического завода

В процессе исследования произведен расчет нагрузок трансформаторного и базы в целом с применением различных методов, выбор метода расчета производился на основе исходных данных, а также осуществлен выбор оборудования и его проверка при различных режимах работы. В результате исследования была спроектирована конкретная модель электроснабжения базы по обслуживанию нефтегазодобывающего месторождения, представлена ее экономическая целесообразность и безопасность для окружающей среды.In the process of studying the calculation of the load and base as a whole with the use of various methods, the choice of the calculation method on the basis of the initial data, and also the selection of equipment and its verification under various operating modes was carried out. As a result of the research, a specific model of power supply for the oil and gas industry maintenance base, its economic feasibility and safety for the environment was designed

Proteomic analysis of the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease

So far, only the detection of 14-3-3 proteins in cerebrospinal fluid (CSF) has been accepted as diagnostic criterion for Creutzfeldt-Jakob disease (CJD). However, this assay cannot be used for screening because of the high rate of false-positive results, whereas patients with variant CJD are often negative for 14-3-3 proteins. The aim of this study was to compare the spot patterns of CSF by 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) to search for a CJD-specific spot pattern. We analyzed the CSF of 28 patients {[}11 CJD, 9 Alzheimer's disease ( AD), 8 nondemented controls (NDC)] employing 2D-PAGE which was optimized for minimal volumes of CSF (0.1 ml; 7-cm strips). All samples were run at least three times, gels were silver stained and analyzed by an analysis software and manually revised. We could consistently match 268 spots which were then compared between all groups. By the use of 5 spots, we were able to differentiate CJD from AD or NDC with a sensitivity of 100%. CJD could also be distinguished from both groups by using a heuristic clustering algorithm of 2 spots. We conclude that this proteomic approach can differentiate CJD from other diseases and may serve as a model for other neurodegenerative diseases. Copyright (C) 2007 S. Karger AG, Basel

Detection and quantification of Aβ−3–40 (APP669‐711) in cerebrospinal fluid

Neurochemical biomarkers can support the diagnosis of Alzheimer’s disease and may facilitate clinical trials. In blood plasma, the ratio of the amyloid-β (Aβ) peptides Aβ−3– 40/Aβ1–42 can predict cerebral amyloid-β pathology with high accuracy (Nakamura et al., 2018). Whether or not Aβ−3–40 (aka. amyloid precursor protein (APP) 669– 711) is also present in cerebrospinal fluid (CSF) is not clear. Here, we investigated whether Aβ−3–40 can be detected in CSF and to what extent the CSF Aβ−3–40/Aβ42 ratio is able to differentiate between individuals with or without amyloid-β positron emission tomography (PET) evidence of brain amyloid. The occurrence of Aβ−3–40 in human CSF was assessed by immunoprecipitation followed by mass spectrometry. For quantifying the CSF concentrations of Aβ−3–40 in 23 amyloid PET- negative and 17 amyloid PET- positive subjects, we applied a sandwich-type immunoassay. Our findings provide clear evidence of the presence of Aβ−3–40 and Aβ−3–38 in human CSF. While there was no statistically significant difference in the CSF concentration of Aβ−3–40 between the two diagnostic groups, the CSF Aβ−3–40/Aβ42 ratio was increased in the amyloid PET- positive individuals. We conclude that Aβ−3– 40 appears to be a regular constituent of CSF and may potentially serve to accentuate the selec- tive decrease in CSF Aβ42 in Alzheimer's disease

Transcriptomic analysis reveals an association of FCGBP with Parkinson’s disease

Transcriptomics in Parkinson’s disease (PD) offers new insights into the molecular mechanism of PD pathogenesis. Several pathways, such as inflammation and protein degradation, have been identified by differential gene expression analysis. Our aim was to identify gene expression differences underlying the disease etiology and the discovery of pre-symptomatic risk biomarkers for PD from a multicenter study in the context of the PROPAG-AGEING project. We performed RNA sequencing from 47 patients with de novo PD, 10 centenarians, and 65 healthy controls. Using identified differentially expressed genes, functional annotations were assigned using gene ontology to unveil significant enriched biological processes. The expression of 16 selected genes was validated using OpenArray® assays and samples from independent cohorts of 201 patients with advanced PD, 340 healthy siblings of PD patients, and 177 healthy controls. Differential gene expression analysis identified higher FCGBP expression in patients with de novo PD compared with healthy controls and compared with centenarians. Furthermore, FCGBP showed no differences in terms of population origin or aging process. The increased FCGBP expression was validated in patients with advanced PD and their siblings. Thus, we provided evidence for an upregulation of FCGBP mRNA levels not only in patients with PD but also in individuals at putative higher risk of PD, suggesting that it could be important in gut–brain PD interaction, mediating the connection between microbiota and intestinal inflammatory processes, as well as neuroinflammation and neurodegeneration