Search results for "tau protein"
showing 10 items of 48 documents
Molecular properties underlying regional vulnerability to Alzheimer’s disease pathology
2018
Amyloid deposition and neurofibrillary degeneration in Alzheimer's disease specifically affect discrete neuronal systems, but the underlying mechanisms that render some brain regions more vulnerable to Alzheimer's disease pathology than others remain largely unknown. Here we studied molecular properties underlying these distinct regional vulnerabilities by analysing Alzheimer's disease-typical neuroimaging patterns of amyloid deposition and neurodegeneration in relation to regional gene expression profiles of the human brain. Graded patterns of brain-wide vulnerability to amyloid deposition and neurodegeneration in Alzheimer's disease were estimated by contrasting multimodal amyloid-sensiti…
Expression of nicotinic acetylcholine receptor subunits in the cerebral cortex in Alzheimer's disease: histotopographical correlation with amyloid pl…
1999
Impairment of cholinergic transmission and decreased numbers of nicotinic binding sites are well-known features accompanying the cognitive dysfunction seen in Alzheimer's disease (AD). In order to elucidate the underlying cause of this cholinoceptive dysfunction, the expression of two pharmacologically different nicotinic acetylcholine receptor (nAChR) subunits (alpha4, alpha7) was studied in the cerebral cortex of Alzheimer patients as compared to controls. Patch-clamp recordings of 14 dissociated neurons of control cortices showed responses suggesting the existence of alpha4- and alpha7-containing functional nAChRs in the human cortex. In cortices of Alzheimer patients and controls, the p…
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…
Genetic linkage of autosomal dominant progressive supranuclear palsy to 1q31.1
2005
Progressive supranuclear palsy (PSP) is a disorder of unknown pathogenesis. Familial clusters of PSP have been reported related to mutations of protein tau. We report the linkage of a large Spanish family with typical autosomal dominant PSP to a new locus in chromosome 1. Four members of this family had typical PSP, confirmed by neuropathology in one case. At least five ancestors had similar disease. Other members of the family have incomplete phenotypes. The power of the linkage analysis was increased by detecting presymptomatic individuals with 18F-fluoro-dopa and 18F-deoxyglucose positron emission tomography. We screened the human genome with 340 polymorphic markers and we enriched the a…
Frontotemporal dementia: the post-tau era.
2006
As scientists have begun to decipher the molecular genetic bases of hereditary frontotemporal dementia (FTD), it has become clear that the biology of these human neurodegenerative diseases has a complexity not previously suspected. FTD has been found to be linked to several chromosomal loci including those in chromosome 9, chromosome 17, and chromosome 3. The article by Guyant-Marechal et al. in this issue of Neurology reports the clinical, pathologic, and molecular characteristics of a form of FTD associated with inclusion body myopathy and Paget disease of the bone observed in members of two families and expands our knowledge on genetically determined FTD.1 The disorder is associated with…
Limited agreement between biomarkers of neuronal injury at different stages of Alzheimer's disease
2013
Abstract New diagnostic criteria for Alzheimer's disease (AD) treat different biomarkers of neuronal injury as equivalent. Here, we quantified the degree of agreement between hippocampal volume on structural magnetic resonance imaging, regional glucose metabolism on positron emission tomography, and levels of phosphorylated tau in cerebrospinal fluid (CSF) in 585 subjects from all phases of the AD Neuroimaging Initiative. The overall chance-corrected agreement was poor (Cohen κ, 0.24–0.34), in accord with a high rate of conflicting findings (26%–41%). Neither diagnosis nor APOE e4 status significantly influenced the distribution of agreement between the biomarkers. The degree of agreement t…
Neocortical Variation of Abeta Load in Fully Expressed, Pure Alzheimer's Disease
2010
The relationship between amyloid-beta (A beta) deposition and tau-related neurofibrillary changes is a key issue in the pathogenesis of Alzheimer's disease (AD). The aim of this study was to investigate the extent and cortical distribution of A beta and tau pathology, their mutual links and their correlation with the duration of the disease in thirty-nine patients with fully expressed AD. By tau immunohistochemistry, we identified different patterns of distribution of neurofibrillary changes that were ascribed to Braak stage V and VI. The disease duration was longer in patients at Braak stage VI than in those at V. Morphometric analysis carried out in several neocortical areas demonstrated …
Association of elevated phospho-tau levels with alzheimer-typical 18F-Fluoro-2-Deoxy-D-Glucose positron emission tomography findings in patients with…
2003
Abstract Background Mild cognitive impairment is considered to be a transitional stage between normal aging and dementia. Phosphorylated tau protein in cerebrospinal fluid and even more decrements of cerebral glucose metabolism in parietal, temporal, or cingulate regions have shown favorable specificity for the diagnosis of Alzheimer dementia and could be useful supplementary tools to determine Alzheimer pathology in early stages. Methods We measured cerebrospinal fluid tau phosphorylated at threonine 181 protein, cerebrospinal fluid total tau, and cerebral glucose metabolism using 18F-fluoro-2-deoxy-D-glucose positron emission tomography in 16 patients with mild cognitive impairment and ag…
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…
Cerebrospinal fluid tau protein is not a biological marker in amyotrophic lateral sclerosis.
2009
Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder leading to progressive motor neuron cell death. Etiopathogenesis is still imperfectly known and much effort have been undertaken to find a biological marker that could help in the early diagnosis and in the monitoring of disease progression. Cerebrospinal fluid (CSF) concentrations of tau, an axonal microtubule-associated protein, have been measured in ALS with levels found increased in some studies and unchanged in others. Methods: Total CSF tau level was assayed in a population of ALS patients (n = 57) and controls (n = 110) using a specific ELISA method. Results: No significant differences in the median CS…