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Raman spectroscopy as the tool for Alzheimer's disease diagnostics
Tesař, Adam ; Kopecký, Vladimír (advisor) ; Jelínek, Otakar (referee)
Alzheimer disease (AD) is the most frequent dementia. The prevalence is approximately 10% in 65 years old people. The current treatment is only progression protective, therefore it is crucial to find a new diagnostic approach for diagnosing AD in early stage. We analysed a set of 55 patients by the drop coating deposition Raman spectroscopy with the goal to verify previously published high sensitivity of the AD spectroscopic diagnosis in cerebral spinal fluid (CSF) and to find a new diagnostic method for blood serum (BS). We optimized measurement conditions for BS. The results were evaluated by the cluster analysis and the principal component analysis. The small set of samples exhibited high sensitivity in both CSF and BS but that distinctly decreased in the whole set. The results for CSF were affected by the choice of the analysed spectral interval. The best for AD diagnose was the interval containing peaks at 980, 1080 and 1249 cm-1.The results for BS have been the most sensitive in the whole spectral range. They have low sensitivity but high specificity for AD (92%). The usage of neural networks has conversely high sensitivity and low specificity in both sets of samples of BS and CSF. Powered by TCPDF (www.tcpdf.org)
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Clinical variability of rare dementias: manifestations and possible reasons
Tesař, Adam ; Rusina, Robert (advisor) ; Baláž, Marek (referee) ; Hort, Jakub (referee)
Clinical variants of dementia are limiting their diagnosis and can leads to underdiagnosing or substitution of two different diseases with the same symptomatology. The aim of this study is a better understanding of a factors involved in the clinical variability of rare dementias. Progressive supranuclear palsy and Gerstmann-Sträussler-Scheinker syndrome caused by mismatch mutation P102L in Prion protein are used as model diseases. In this thesis, we firstly demonstrate the influence of the distribution of neuropathology and its spread on the clinical phenotype of the disease. Although a single neurodegenerative disease increases the risk of neurodegenerative comorbidity, this other neuropathology does not affect the phenotypic presentation of the primary disease. Monogenetically inherited proteinopathies can have a different clinical subtype, which is not only conditioned by causal protein polymorphisms, but can be influenced by the wild type allele of causal protein. A more accurate understanding of the symptomatic variability in dementias will allow a better focus of a drug studies and, in the future a treatment, but it will also lead to a better understanding of the pathogenesis of neurodegenerative diseases. Keywords: dementia, Progressive supranuclear palsy, Gerstmann-Sträussler-Scheinker...
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Raman spectroscopy as the tool for Alzheimer's disease diagnostics
Tesař, Adam ; Kopecký, Vladimír (advisor) ; Jelínek, Otakar (referee)
Alzheimer disease (AD) is the most frequent dementia. The prevalence is approximately 10% in 65 years old people. The current treatment is only progression protective, therefore it is crucial to find a new diagnostic approach for diagnosing AD in early stage. We analysed a set of 55 patients by the drop coating deposition Raman spectroscopy with the goal to verify previously published high sensitivity of the AD spectroscopic diagnosis in cerebral spinal fluid (CSF) and to find a new diagnostic method for blood serum (BS). We optimized measurement conditions for BS. The results were evaluated by the cluster analysis and the principal component analysis. The small set of samples exhibited high sensitivity in both CSF and BS but that distinctly decreased in the whole set. The results for CSF were affected by the choice of the analysed spectral interval. The best for AD diagnose was the interval containing peaks at 980, 1080 and 1249 cm-1.The results for BS have been the most sensitive in the whole spectral range. They have low sensitivity but high specificity for AD (92%). The usage of neural networks has conversely high sensitivity and low specificity in both sets of samples of BS and CSF. Powered by TCPDF (www.tcpdf.org)
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Spectroscopic study of interaction of antimicrobial peptides with model membranes
Tesař, Adam ; Kopecký, Vladimír (advisor) ; Kočišová, Eva (referee)
Antimicrobial peptides (AMP) have a great potential in medicine and pharmacy. Mechanism of their impact is an interaction with a cell membrane leading to the penetration of the membrane. The way of disruption of the cell membrane is not completely understand, therefore we focused on the interaction of AMP HAL-1, isolated from the venom of the bee Halictus sexctinctus, with a model membrane of 100 nm liposomes consisting of phosphatidylcholin and phosphatidylglycerol. Circular dichroism and infrared spectroscopy (FTIR) proved the change of the secondary structure from the random coil of free HAL-1 to -helix in an interaction with the membrane. The next step was preparation of the lipid bilayer on the surface of ATR prism, which will enable usage of the polarized FTIR spectroscopy to study the interaction of AMP with model membranes in future. Therefore, the ATR-FTIR spectroscopy and factor analyses were applied to study dynamics of drying of the liposomes and their subsequent hydration also with an addition of HAL-1. We focused on the stabilization of the system. Hydratation of the lipid bilayer by 2 µl sample showed stability for minutes, nevertheless after dilution the stabilization decay in minutes. The protective influence of the peptide on the lipid bilayer and slowing down of the drying out of the...
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