Search results for "tau protein"
showing 10 items of 48 documents
Obstructive sleep apnea and Alzheimer’s disease-related cerebrospinal fluid biomarkers in mild cognitive impairment
2020
Abstract Previous studies have demonstrated that sleep-breathing disorders, and especially obstructive sleep apnea (OSA), can be observed in patients with a higher risk of progression to Alzheimer’s disease (AD). Recent evidence indicates that cerebrospinal fluid (CSF) AD-biomarkers are associated with OSA. In this study, we investigated these associations in a sample of patients with mild cognitive impairment (MCI), a condition that is considered the first clinical phase of AD, when patients showed biomarkers consistent with AD pathology. A total of 57 patients (mean age = 66.19; SD = 7.13) with MCI were included in the study. An overnight polysomnography recording was used to assess objec…
Apolipoprotein E isoforms and the development of low and high Braak stages of Alzheimer's disease-related lesions
1999
In recent research, apolipoprotein-E (apoE) polymorphism has been shown to influence the formation of neurofibrillary changes and the accumulation of beta/A4-amyloid, the histopathological hallmarks of Alzheimer's disease (AD). Clinical studies associate the apoE allele epsilon4 with earlier onset of the disease, although the clinical speed of progression remains unchanged. Time course estimates have also provided evidence which indicates that the clinical phase of AD constitutes only 10-20% of the total time span needed for the development of this slowly progressing degenerative brain disorder. Due to the lack of reliable clinical tests for the detection of pre-symptomatic stages of AD, we…
The pathological hallmarks of Alzheimer’s disease derive from compensatory responses to NMDA receptor insufficiency
2018
AbstractAlzheimer’s disease is characterized by intracellular aggregates of hyperphosphorylated tau protein and extracellular plaques of amyloid β peptide, a product of APP processing. The origin of these pathological hallmarks has remained elusive. Here, we have tested the idea that both alterations, at the onset of the disease, may constitute compensatory responses to the same causative and initial trigger, namely NMDA receptor insufficiency. Treatment of rat cortical neurons with the specific NMDA receptor antagonist AP5 within 4 h caused a significant increase in tau phosphorylation at the AT8 and S404 epitopes as well as an increase in APP expression and Aβ 40 secretion. Single intrape…
Alzheimer’s disease and infections, where we stand and where we go
2014
Editorial Alzheimer’s disease (AD) is a progressive neurological disorder, which represents the most common form of dementia, one of the major causes of disability in later life. Age is the greatest risk factor for AD, which typically affects people aged 65 years and over, with an age-standardised prevalence of 4.4 [1]. However, AD is not a normal part of ageing and advanced age alone does not justify the disease. Several pathways have been implicated in AD pathophysiology, the most described is the neurodegenerative one, which lead to the brain accumulation of beta-amyloid and neurofibrillary tangles, aggregations of hyperphosphorylated tau protein, macroscopically resulting in brain atrop…
Deciphering Alzheimer’s Disease Pathogenic Pathway: Role of Chronic Brain Hypoperfusion on p-Tau and mTOR
2021
This review examines new biomolecular findings that lend support to the hemodynamic role played by chronic brain hypoperfusion (CBH) in driving a pathway to Alzheimer’s disease (AD). CBH is a common clinical feature of AD and the current topic of intense investigation in AD models. CBH is also the basis for the vascular hypothesis of AD which we originally proposed in 1993. New biomolecular findings reveal the interplay of CBH in increasing tau phosphorylation (p-Tau) in the hippocampus and cortex of AD mice, damaging fast axonal transport, increasing signaling of mammalian target of rapamycin (mTOR), impairing learning-memory function, and promoting the formation of neurofibrillary tangles…
Klinische Aspekte der "argyrophilic grain disease"
2000
Argyrophilic grain disease (AGD) is a frequently occurring degenerative illness of the aging human brain. It is accompanied by progressive pathological alterations of the cytsokeleton which are traceable to an abnormal phosphorylation of the microtubule associated tau protein. Histologically, it is possible with the help of suitable staining techniques to identify pathognomonic spindle-shaped cellular inclusions (argyrophilic grains). These cellular inclusions display a typical cortical as well as subcortical distribution pattern. The goal of the present study is the retrospective evaluation of the clinical findings from 53 individuals with neuropathologically demonstrable AGD-related chang…
Aβ and tau toxicities in Alzheimer’s are linked via oxidative stress-induced p38 activation: Protective role of vitamin E
2014
AbstractOxidative stress is a hallmark of Alzheimer’s disease (AD). We propose that rather than causing damage because of the action of free radicals, oxidative stress deranges signaling pathways leading to tau hyperphosphorylation, a hallmark of the disease. Indeed, incubation of neurons in culture with 5 µM beta-amyloid peptide (Aβ) causes an activation of p38 MAPK (p38) that leads to tau hyperphosphorylation. Inhibition of p38 prevents Aβ-induced tau phosphorylation. Aβ-induced effects are prevented when neurons are co-incubated with trolox (the water-soluble analog of vitamin E).We have confirmed these results in vivo, in APP/PS1 double transgenic mice of AD. We have found that APP/PS1 …
NOVEL SMALL MOLECULES THAT BIND AND/OR MODULATE DIFFERENT FORMS OF TAU OLIGOMERS
2020
The present invention relates to novel small molecules of Formulas I, II, III, IIIa, IIIb, and IV and pharmaceutically acceptable salts thereof, as well as the preparation and the use thereof.
Azure C Targets and Modulates Toxic Tau Oligomers.
2018
Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder affecting millions of people worldwide. Therefore, finding effective interventions and therapies is extremely important. AD is one of over 20 different disorders known as tauopathies, characterized by the pathological aggregation and accumulation of tau, a microtubule-associated protein. Tau aggregates are heterogeneous and can be divided into two major groups: large metastable fibrils, including neurofibrillary tangles, and oligomers. The smaller, soluble and dynamic tau oligomers have been shown to be more toxic with more proficient seeding properties for the propagation of tau pathology as compared to the …
Assessment of cerebral microbleeds by susceptibility-weighted imaging in Alzheimer's disease patients: A neuroimaging biomarker of the disease.
2017
Purpose The objective of this study was to correlate the presence and distribution of cerebral microbleeds in Alzheimer’s disease patients with cerebrospinal fluid biomarkers (amyloid-beta and phosphorylated tau 181 protein levels) and cognitive decline by using susceptibility-weighted imaging magnetic resonance sequences at 1.5 T. Material and methods Fifty-four consecutive Alzheimer’s disease patients underwent brain magnetic resonance imaging at 1.5 T to assess the presence and distribution of cerebral microbleeds on susceptibility-weighted imaging images. The images were analyzed in consensus by two neuroradiologists, each with at least 10 years’ experience. Dementia severity was assess…