The calcium hypothesis of neurodegenerative disorders such as Alzheimer´s disease (AD) suggests that altered cytosolic Ca2+ levels ([Ca2+]i) and/or disturbances in Ca2+ homeostasis concern cellular mechanisms underlying neuronal pathology. To search for a diagnostic marker of Alzheimer´s disease, we measured cytosolic calcium concentrations in platelets of AD patients, age-matched control subjects (AMC), and vascular dementia (VD) patients. The ([Ca2+]i) was determined using long wavelength indicator Fluo-3AM in 21 mild AD patients, 17 AMC, and 23 patients with VD. The basal values of [Ca2+]i were significantly lower in AD compared to AMC. After the addition of 1 mM calcium, the [Ca2+]i markedly increased in platelets of AD compared to AMC and VD. Measurement of calcium homeostasis could provide a very sensitive, but less specific biological marker of AD. These results support the hypothesis that influencing calcium homeostasis may provide a therapeutic strategy in dementia.
Senile dementia of Alzheimer´s type (AD) is commonly characterized as a neurodegenerative disorder, which exhibits gradual changes of consciousness, loss of memory, perception and orientation as well as loss of personality and intellect. AD prevalence increases dramatically with age and is the fourth cause of death in Europe and in the USA. Currently, there are no available biological markers, which gives clinicians no other alternative than to rely upon clinical diagnosis by exclusion. There is no assay of objective ante mortem biochemical phenomena that relate to the pathophysiology of this disease. The pathophysiology of AD is connected with alterations in neurotransmission, plaque formation, cytoskeletal abnormalities and disturbances of calcium homeostasis. The search for a test, which is non-invasive, simple, cheap and user-friendly, should be directed at accessible body fluids. Only abnormalities replicated in large series across different laboratories fulfilling the criteria for a biological marker are likely to be of relevance in diagnosing AD. To date, only the combination of cerebrospinal fluid t and Ab42 most closely approximate an ideal biomarker of Alzheimer´s disease. A short review on the role of biological markers in AD on the basis of the literature, contemporary knowledge and our own recent findings are presented., D. Řípová, A. Strunecká., and Obsahuje bibliografii
Objective: The anxiety of Alzheimer's disease (AD) contributes significantly to decreased quality of life, increased morbidity, higher levels of caregiver distress, and the decision to institutionalize a patient. However, the incidence of anxiety in AD patients hasn't been discussed. In this study, artificial neural networks were used to predict the incidence of anxiety inAD patients.
Methods: A large randomized controlled clinical trial was analyzed in this study, which involved AD patients and caregivers from 6 different sites in the United States. The incidence of anxiety in AD patients was predicted by backpropagation artificial neural networks with one and hidden layers. After cross validation, the Predictive Accuracy (PA) of the models was measured to select the best structure of artificial neural networks.
Results: Among all models for predicting the incidence of anxiety in AD patients, the artificial neural network with respectively 6 and 3 neurons in the first and second hidden layers achieved the highest predictive accuracy of 85.56%.
Conclusions: The incidence of anxiety in AD patients can be predicted by an accuracy of over 80%. When used for anxiety prediction, neural networks with two hidden layers perform better than those with one hidden layer. These findings will benefit the prevention and early intervention of anxiety in Alzheimer's patients.
Acetylcholinesterase (AChE) inhibitors represent standard treatment of Alzheimer´s disease. Cholesterol plays an important role in Alzheimer´s disease development. Because cholesterol synthesis may be inhibited by statins or bisphosphonates, we hypothesized that these drugs might possibly have an influence on cholinesterases. Moreover, we also evaluated if the cholesterol-lowering agents that cross the blood-brain barrier (e.g. simvastatin) should be more effective than those which do not (e.g. atorvastatin). Four groups of rats were orally administered simvastatin, atorvastatin, alendronate or vehicle for seven days. Thereafter, blood samples were taken and the basal ganglia, septum, frontal cortex, and hippocampus were isolated from brains for measurement of acetylcholinesterase activity. In the blood, activities of neither acetyl- nor butyrylcholinesterase were influenced by any of the applied drugs. In the brain, no significant changes in AChE activity were observed after administration of atorvastatin. Both simvastatin and alendronate significantly suppressed the activity of AChE in the frontal cortex. In conclusion, our results confirmed the hypothesis that cholesterol-modifying drugs modulate AChE activity and it is more reasonable to use a blood-brain barrier penetrating drug., Ľ. Cibičková, V. Palička, N. Cibiček, E. Čermáková, S. Mičuda, L. Bartošová, D. Jun., and Obsahuje bibliografii a bibliografické odkazy
The Laboratory of Neurophysiology of Memory started its existence in 1954 by systematic research into spreading depression of EEG activity of laboratory rodents and by the use of this remarkable phenomenon as a functional ablation method in behavioral research. Its main contributions were in the study of memory formation and consolidation, interhemispheric transfer, motor learning, conditioned taste aversion and spatial orientation and navigation. In the last five years it concentrated on navigation of rats in multiple reference frames, on electrophysiological evidence for the role of hippocampal place cells support of behavior in such dissociated frames, on the analysis of idiothetic and allothetic forms of navigation and on the mathematical methods allowing assessment of the contribution of goal directed locomotion to place cell activity. The methods used in spatial memory research in rats were used for examination of human subjects in a laboratory equipped with a tracking system for humans in the hospital Homolka. Animal models of Alzheimer disease were studied in transgenic mice with the human gene for the beta amyloid precursor protein.
Alzheimer’s disease (AD) is a primary cause of dementia in the middle-aged and elderly worldwide. Animal models for AD are widely used to study the disease mechanisms as well as to test potential therapeutic agents for disease modification. Among the non-genetically manipulated neuroinflammation models for AD, lipopolysaccharide (LPS)-induced animal model is commonly used. This review paper aims to discuss the possible factors that influence rats’ response following LPS injection. Factors such as dose of LPS, route of administration, nature and duration of exposure as well as age and gender of animal used should be taken into account when designing a study using LPS-induced memory impairment as model for AD., R. Zakaria, W. M. H. Wan Yaacob, Z. Othman, I. Long, A. H. Ahmad, B. Al-Rahbi., and Obsahuje bibliografii
Peripheral insulin resistance is associated with decreasing adiponectin and increasing leptin plasma levels, and also with cognitive decline. The effects of adipokines on brain function have been published from both animal and human studies. In particular, the influence of leptin and adiponectin on the development of Alzheimer’s disease (AD) has been extensively investigated. However, the association between adipsin and AD is as yet unknown. In 37 patients with AD and 65 controls that followed the same study protocol, we tested whether adiponectin, leptin, and adipsin could be used as biomarkers in the early stages of AD. In contrast with conclusions of cognition studies in insulin resistant states, our study found a correlation of impaired neuropsychological performance with increasing adiponectin and decreasing leptin in AD patients. Nevertheless, no significant differences between patients and controls were found. AD women had significantly increased adipsin compared to controls, and there was a positive correlation of adipsin with age and disease duration. Although adipokines do not appear to be suitable biomarkers for early AD diagnosis, they certainly play a role in the pathogenesis of AD. Further studies will be needed to explain the cause of the adipokine “breaking point” that leads to the pathogenesis of overt AD., Markéta Vaňková, Gabriela Vacínová, Josef Včelák, Daniela Vejražková, Petra Lukášová, Robert Rusina, Iva Holmerová, Eva Jarolímová, Hana Vaňková, Běla Bendlová., and Obsahuje bibliografii
Steroids are important components in the pathophysiology of Alzheimer’s disease (AD). Although their role has been studied, the corresponding metabolomic data is limited. In the present study we evaluate the role of steroid sulfotransferase SULT2A1 in the pathophysiology of AD on the basis of circulating steroids (measured by GC-MS), in which the sulfation catalyzed by SULT2A1 dominates over glucuronidation (pregnenolone/sulfate, DHEA/sulfate, androstenediol/sulfate and 5α-reduced pregnane and androstane catabolites). To estimate a general trend of SUL2A1 activity in AD patients we compared the ratios of steroid conjugates to their unconjugated counterparts (C/U) in controls (11 men and 22 women) and AD patients (18 men and 16 women) for individual circulating steroids after adjustment for age and BMI using ANCOVA model including the factors AD status and gender. Decreased C/U ratio for the C19 steroids demonstrate an association between attenuated sulfation of C19 steroids in adrenal zona reticularis and the pathophysiology of AD., M. Vaňková, M. hill, M. Velíková, J. Včelák, G. Vacínová, P. Lukášová, D. Vejražková, K. Dvořáková, R. Rusina, I. Holmerová, E. Jarolímová, H. Vaňková, B. Bendlová., and Obsahuje bibliografii
The new method is based on non-linear one-step predictor, which is designed as MLP neural network. It is a kind of low-pass non-linear filter. The difference between raw EEG and the ANN output is then a subject of band spectral analysis. The differences in this power spectrum between Alzheimer's diseased and control patient group are statistically significant.