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Mitophagy biomarkers in the continuum of Alzheimer's disease
Katonová, Alžbeta ; Veverová, Kateřina (advisor) ; Bohačiaková, Dáša (referee)
The findings of recent years have shown that impaired mitophagy is involved in the pathophysiology of Alzheimer's disease (AD) and other neurodegenerative diseases. Studies on brain biopsies of AD patients, cellular and animal models of AD show that age-dependent decline in mitophagy is a significant contributor to AD pathology, and that the levels of mitophagy proteins are altered. However, whether these changes are reflected in the biofluids of individuals with AD, and whether mitophagy proteins could be potential biomarkers of AD, is unknown.The aim of the diploma thesis was to compare the level of mitophagy markers in blood serum and cerebrospinal fluid (CSF) of patients in various stages of AD with cognitively healthy controls (CU) and determine its relationship to the degree of cognitive impairment and standard Alzheimer's biomarkers (amyloid beta (Ab42), total tau (T-tau) and tau phosphorylated at threonine 181 (P-tau181)). We have shown that mitophagy is impaired in individuals with AD, manifested by increased levels of PINK1 and BNIP3L (activators of mitophagy) and decreased levels of TFEB (master regulator of lysosomal biogenesis) compared to CU. Moreover, these changes were associated with more advanced AD pathology, manifested by increased AD biomarker positivity and cognitive...
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Biofluid biomarkers of Alzheimer's disease and Lewy body disease and their relationship with cognitive and structural markers
Jurášová, Vanesa ; Veverová, Kateřina (advisor) ; Chmátalová, Zuzana (referee)
The diagnosis of Alzheimer's disease is based on the determination of specific proteins in cerebrospinal fluid (CSF) or their imaging using positron emission tomography. Both methods are invasive and can expose the patient to risk and discomfort. Blood biomarkers, therefore, represent hope for early diagnosis and monitoring of individuals at increased risk of developing Alzheimer's disease. The diploma thesis aimed to determine biomarkers in blood using the ultrasensitive Simoa TM (Single molecular assay) technology and to verify their relationship to the values in CSF. The second aim was to track the relationship between blood biomarkers and cognitive markers of Alzheimer's disease. We demonstrated a positive relationship between serum, plasma, and CSF p-tau 181 concentrations. A negative correlation was observed between the concentrations of p-tau 181 in blood and the results of the MMSE test, which is considered a standard cognitive assessment tool. These findings suggest that plasma and serum p-tau 181 may greatly help the clinical identification of neurodegenerative diseases in primary care. The negative correlation of plasma and serum p-tau 181 with MMSE test results suggests that blood p-tau 181 could be used in population-based studies to detect individuals at high risk of developing...
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