Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixteen brains from Alzheimer's disease (AD) patients with varying duration of dementia were studied using the monoclonal antibody (mAb) 6.423 raised against the three repeated domains of the tau protein, and named the paired helical filament (PHF) core. In Ammon's horns of the AD cases 6.423 mAb, in addition to immunoreacting with neurofibrillary tangles (NFTs), dystrophic neurites, and plaquelike structures, also recognized a subpopulation of granulovacuolar degeneration elements (GVD). A new immunoreactive structure, a spherical inclusion, was also stained by 6.423. The immunoreactive GVD elements and the spherical inclusion were found in the aged controls (greater than 65 years of age) and in non-AD dementia cases, as well. The staining of the GVD was markedly decreased when the tissue was preincubated with alkaline phosphatase. In contrast, NFTs and the spherical inclusions resisted dephosphorylation. Neurons containing the spherical inclusion frequently lacked immunoreactive intracellular NFTs. Due to the similar immunohistochemical properties between the spherical bodies and immunoreactive NFTs, we named this new inclusion PHF core body. Our results suggest that the PHF core body may represent a successful attempt by hippocampal neurons to restrict the PHF core expression. Thus, the failure of this mechanism may lead to the NFT formation in a range of dementing processes. Alternatively, the PHF core body may be an early stage in the NFT formation.
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PMID:New patterns of intraneuronal accumulation of the microtubular binding domain of tau in granulovacuolar degeneration. 132 97

The neuropathological changes seen in Alzheimer's disease represent an interaction between the ageing process in which normal intellectual function is retained, and changes which are specifically associated with severe cognitive deterioration. Molecular analysis of these changes has tended to emphasize the distinction between neurofibrillary pathology, which is intracellular and highly correlated with cognitive deterioration, and the changes associated with the deposition of extracellular amyloid, which appears to be widespread in normal ageing. Extracellular amyloid deposits consist of fibrils composed of a short 42 amino acid peptide (beta/A4) derived by abnormal proteolysis from a much larger precursor molecule (APP). The recent demonstration of a mutation associated with APP in rare cases with familial dementia, neurofibrillary pathology in the hippocampus and atypical cortical Lewy body pathology raises the possibility that abnormal processing of APP could be linked directly with neurofibrillary pathology. Neurofibrillary tangles and neuritic plaques are sites of dense accumulation of pathological paired helical filaments (PHFs) which are composed in part of an antigenically modified form of the microtubule-associated protein tau. The average brain tissue content of PHFs measured biochemically does not increase in the course of normal ageing but increases 10-fold relative to age-matched controls in patients with Alzheimer's disease. There is also a substantial (three-fold) disease-related decline in normal soluble tau protein relative to age-matched controls. This intracellular redistribution of a protein essential for microtubule stability in cortico-cortical association circuits may play an important part in the molecular pathogenesis of dementia in Alzheimer's disease. The role of abnormal proteolysis of APP in this process remains to be elucidated. Immunohistochemical studies on renal dialysis cases have failed to detect evidence of neurofibrillary pathology related to aluminium accumulation in brain tissue. Nevertheless it needs to be seen whether more sensitive biochemical assays of neurofibrillary pathology can demonstrate evidence of an association with aluminium.
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PMID:Molecular characterization and measurement of Alzheimer's disease pathology: implications for genetic and environmental aetiology. 149 Apr 26

The immunohistochemical and ultrastructural characteristics of spinal cord neurofibrillary tangles (NFTs) were examined in Guamanian amyotrophic lateral sclerosis and in parkinisonism-dementia complex on Guam. The spinal cord NFTs reacted with antibodies to tau protein (tau-2), ubiquitin and paired helical filaments (PHFs). Ultrastructurally, the components of the NFTs were seen as randomly arranged fibrils which were often associated with osmiophilic granules; small bundle-like arrangements were also occasionally observed. Individual NFT fibrils appeared as straight fibrils with a diameter of approximately 15 nm and constricted fibrils with a periodicity of approximately 80 nm. Ultrastructural microscopic examination of specimens stained by the modified Bielschowsky method and with the antibodies revealed silver particles and the products of the tau, ubiquitin and PHF immunoreactions on the NFT fibrils. This is the first demonstration of the fine structure of the spinal cord NFTs.
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PMID:Ultrastructural identification of neurofibrillary tangles in the spinal cords in Guamanian amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam. 155 58

The incidence of amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia complex (PDC) among the Chamorros in Guam is remarkably high. The patients with ALS have clinical and pathological characteristics similar to those in other parts of the world. The PDC patients display parkinsonism and progressive dementia and show a characteristic neuronal loss in certain parts of the central nervous system such as the hippocampus and substantia nigra. The Guamanian patients with ALS and PDC commonly have widespread Alzheimer's neurofibrillary changes, but without the associated senile plaques. We have applied immunohistochemical procedures to examine the expression of marker substances in Guamanian ALS and PDC. The markers studied include tau protein, ubiquitin, beta proteins, synaptophysin, calcineurin, Met-enkephalin, substance P and tyrosine hydroxylase. The results were compared with the findings in patients with Alzheimer's disease, Parkinson's disease, sporadic ALS and familial ALS.
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PMID:Amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam: immunohistochemical studies. 158 17

The most characteristic cellular change in Alzheimer's disease is the accumulation of aberrant filaments, the paired helical filaments (PHF), in the affected neurons. There is growing evidence from a number of laboratories that dementia correlates better with the accumulation of PHF than of the extracellular amyloid, the second major lesion of Alzheimer's disease. PHF are both morphologically and biochemically unlike any of the normal neurofibrils. The major polypeptides in isolated PHF are microtubule-associated protein tau. Tau in PHF is phosphorylated differently from tau in microtubules. This abnormal phosphorylation of tau in PHF occurs at several sites. The accumulation of abnormally phosphorylated tau in the affected neurons in Alzheimer's disease brain precedes both the formation and the ubiquitination of the neurofibrillary tangles. In Alzheimer's disease brain, tubulin is assembly competent, but the in vitro assembly of microtubules is not observed. In vitro, the phosphate groups in PHF are less accessible than those of tau to alkaline phosphatase. The in vitro dephosphorylated PHF polypeptides stimulate microtubule assembly from bovine tubulin. It is hypothesized that a defect in the protein phosphorylation/dephosphorylation system is one of the earliest events in the cytoskeletal pathology in Alzheimer's disease. Production of nonfunctional tau by its phosphorylation and its polymerization into PHF most probably contributes to a microtubule assembly defect, and consequently, to a compromise in both axoplasmic flow and neuronal function. Index Entries: Alzheimer's disease; mechanisms of neuronal degeneration; neurofibrillary changes; paired helical filaments: biochemistry; microtubule-associated protein tau; abnormal phosphorylation; ubiquitination; microtubule assembly; axoplasmic flow; protein phosphorylation/dephosphorylation.
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PMID:Ubiquitination and abnormal phosphorylation of paired helical filaments in Alzheimer's disease. 172 45

A histopathological study was carried out on the brains of eight ex-boxers (ages 56 to 83) using conventional histological staining methods and immunocytochemistry with antibodies to amyloid beta-protein and the PHF-related tau protein. All cases showed a large number of tau-immunoreactive neurofibrillary tangles and also beta-protein immunoreactive senile plaques in the cortex. In the areas with many neurofibrillary tangles, neuropil threads with tau-immunoreactivity were also observed, and some of the senile plaque lesions were surrounded by abnormal neurites with tau-immunoreactivity. Moreover, three cases revealed beta-protein-type cerebrovascular amyloid deposits on both leptomeningeal and cortical blood vessels. The present observations indicate that the cerebral pathology of dementia pugilistica is very similar to that of Alzheimer's disease and suggest that these two disorders share some common etiological and pathogenic mechanisms.
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PMID:Re-examination of ex-boxers' brains using immunohistochemistry with antibodies to amyloid beta-protein and tau protein. 175 60

Previous studies of Alzheimer's disease (AD) have correlated the severity of dementia with either the number of senile plaques or neurofibrillary tangles. We used antibodies raised against amyloid beta/A4 protein of senile plaque cores and tau protein as well as thioflavine S and the Campbell-Switzer modification of the Hicks silver method to examine the hippocampal formation and five neocortical regions from 22 nondemented elderly control subjects and 34 demented patients with cerebral senile plaques and neurofibrillary tangles, without complicating disease processes. Ten control subjects (46%) had no beta/A4 protein deposition. Twelve control subjects (54%) had widespread beta/A4 protein deposition but no neocortical neuritic pathology. Of the 34 patients with AD-type changes, 27 (79%) had widespread senile plaques and neurofibrillary tangles, while 7 (21%) had neocortical senile plaques with few neurofibrillary tangles. All demented patients had widespread beta/A4 protein deposition and neocortical tau-immunoreactive, Hicks silver-positive dystrophic neurites. The neurites were found both free in the neuropil as well as surrounding senile plaques. Quantitative analysis showed that dystrophic neurites were significantly increased in patients with AD compared with control subjects and the number of dystrophic neurites and neurofibrillary tangles correlated with the clinical severity of dementia. Widespread cerebral beta/A4 protein deposition may be necessary but by itself is insufficient for the development of dementia in AD.
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PMID:Neuritic pathology and dementia in Alzheimer's disease. 191 Feb 74

This investigation concerns the expression of paired helical filaments, tau protein, ubiquitin, beta-amyloid protein, and synaptophysin in the hippocampus of patients with parkinsonism-dementia complex on Guam (PDC) and Alzheimer's disease. Alzheimer's neurofibrillary tangles (NFTs) were identified in all cases of PDC and Alzheimer's disease by the modified Bielschowsky method, with which they were readily detected, and by immunohistochemical procedures using antibodies to paired helical filaments, tau protein, and ubiquitin. Observations regarding the different morphological stages indicated that NFTs were similar in PDC and Alzheimer's disease. The same markers were also useful for detecting neuropil threads, abundant in the CA1 field and the subiculum in both diseases. In the CA4 region of some PDC cases, prominent threads were noted. No senile plaques or amyloid angiopathies were seen in the hippocampus of the PDC cases examined. There was a significant decrease in synaptophysin immunoreactivity, most pronounced in the subfield CA1 and the subiculum, as well as in the outer molecular layer of the dentate gyrus, in both disorders.
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PMID:Immunohistochemical study of the hippocampus in parkinsonism-dementia complex on Guam. 195 65

A man, aged 58 years, suffered from progressive dementia, parkinsonism, and gaze paralysis for 30 months. Autopsy revealed severe degeneration of the substantia nigra, numerous swollen chromatolytic neurons within the cerebral cortex, scattered basal neurofibrillary tangles, and gliosis of the cerebral white matter and basal ganglia. Unusual globular inclusions positive for tau protein were detected within neurons of the upper cortical layers. Although the pathological findings were comparable with corticonigral degeneration with neuronal achromasia, several clinical and pathological features characteristic for progressive supranuclear palsy, progressive subcortical gliosis, and Pick's disease in this and the nine previously reported cases hampered the unequivocal nosological placement.
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PMID:Corticonigral degeneration with neuronal achromasia and basal neurofibrillary tangles. 208 97

The microtubule-associated protein tau is present in the pathologic hallmarks of Alzheimer's disease and its production and deposition have been implicated in the pathogenesis of the disease. We detected tau mRNA using in situ hybridization histochemistry in the hippocampus, visual cortex, and cerebellum, and compared its level in Alzheimer's disease with controls. The amount of tau mRNA also was determined as a ratio of total polyadenylated mRNA in each area. A significant and gene-specific increase in tau mRNA hybridization was found in hippocampal fields CA4 and CA3, with a similar trend in the dentate gyrus. In contrast, no change was found in the visual cortex or cerebellum in Alzheimer's disease. Increased hippocampal expression of tau mRNA also was present in cases of non-Alzheimer's dementia. Enhanced tau mRNA may be a marker of attempted plasticity involving the cytoskeleton in neuronal populations affected by various neurodegenerative disorders.
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PMID:Increased tau messenger RNA in Alzheimer's disease hippocampus. 211 43


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