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)

Post-mortem neuropathological examination of five cases of Niemann-Pick disease type C revealed neurofibrillary tangles in many parts of the brain. Tangles were a consistent finding in the hippocampus, hypothalamus, substantia innominata, midbrain pons and medulla. Other regions of the brain in which tangles were present included neocortex, basal ganglia, thalamus, cerebellar cortex in one case, and dentate nucleus in another. The tangles were argyrophilic, fluoresced under ultraviolet light when stained with thioflavin S, and reacted strongly with antibody to tau protein. Some of the tangles could be immunostained for ubiquitin. Electron microscopy, performed in one of the cases, showed the tangles to consist of paired helical filaments ultrastructurally identical to those of Alzheimer's disease. The distribution of the tangles in the central nervous system as a whole and also within many individual neurons corresponded fairly closely with that of the abnormal storage material. Both the tangles and the storage material extended into, and distended, the proximal parts of many dendrites and axons. No A4/beta protein, either in the form of plaques or in the walls of blood vessels, was detected in any of the cases. Our findings suggest that neurofibrillary tangles are a common feature of Niemann-Pick disease type C and that their formation may be a reaction to the abnormal storage material.
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PMID:Neurofibrillary tangles in Niemann-Pick disease type C. 789 98

Ubiquitin-immunoreactive dystrophic neurites in the CA2/3 region of the hippocampus are characteristic of diffuse Lewy body disease (DLBD). The origin of dystrophic CA2/3 neurites is unknown, but their extent correlates with the number of cortical Lewy bodies (LBs). To examine the molecular composition of these lesions, hippocampal sections were obtained at postmortem from cases of DLBD, Parkinson's disease and Alzheimer's disease. The tissue samples were fixed in a variety of fixatives and immunostained with antibodies to ubiquitin, ubiquitin C-terminal hydrolase (PGP9.5), neurofilament protein subunits, tau protein, paired helical filaments and tyrosine hydroxylase (TH). In addition to being ubiquitin positive, both cortical LBs and CA2/3 dystrophic neurites were positive with a neurofilament monoclonal antibody (RM032) and PGP9.5; however, fewer lesions were detected with these antibodies compared to ubiquitin immunocytochemistry. The dystrophic CA2/3 neurites were not stained with antibodies to tau proteins, paired helical filaments or TH. Absence of TH immunoreactivity suggests that CA2/3 neuritic processes are not derived from brain stem dopaminergic afferents to the hippocampus. Since CA2/3 neurites are immunologically similar to cortical LB, the pathogenesis of these lesions may be similar. Characterization of dystrophic CA2/3 neurites and cortical LBs may clarify how these lesions contribute to the emergence of dementia in DLBD.
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PMID:Immunoreactivity profile of hippocampal CA2/3 neurites in diffuse Lewy body disease. 791 27

The cytoskeletal abnormalities of cortical neurons in human cerebral cortical dysplasia were compared by immunohistochemical methods to the neurofibrillary tangles of Alzheimer's disease (AD). Surgical specimens from cortical resections performed for the treatment of intractable childhood seizures as well as autopsied samples from AD patients were analyzed with different antibodies directed against high- or medium-molecular mass neurofilament epitopes, phosphorylated or non-phosphorylated forms of neurofilaments, ubiquitin, the microtubule-associated protein tau, and paired helical filaments (PHF), a defining feature of AD tangles. A strong abnormal increase in immunoreactivity to the high and medium molecular mass neurofilament epitopes was seen in hypertrophic neurons of cortical dysplasia. These neurofilamentous accumulations of cortical dysplasia as well as AD tangles also displayed immunoreactivity with antibodies against phosphorylated and non-phosphorylated neuro-filament epitopes, tau and ubiquitin. Only the AD tangles, however, were immunoreactive to the antiserum to PHF. These results replicate and extend our previous findings that the neurofibrillary accumulations in cerebral cortical dysplasia share some common antigens with the neurofibrillary tangles of AD but do not demonstrate immunoreactivity to PHF antiserum. The results also suggest that the cytoskeletal abnormalities observed in neurons of cortical dysplasia may result in part from alterations in the level of expression, in phosphorylation state or in transport of cytoskeletal components.
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PMID:Neuronal cytoskeletal abnormalities in human cerebral cortical dysplasia. 805 2

Excessive stimulation of glutamate receptors and elevation of intracellular calcium levels initiate the neurodegenerative process resulting from cerebral ischemia. However, the subsequent cascade of molecular changes which are of pathogenic significance is less well understood. Breakdown of the cytoskeleton may be involved in the progression from compromise of neuronal viability to irreversible damage. Alteration of the microtubule-associated protein tau, as reflected by increased Alz-50 immunoreactivity, was induced by permanent focal cerebral ischemia in vivo but only in a proportion of neurones. Alz-50 immunoreactive neurones did not exhibit the characteristics of irreversible ischemic cell damage. Increased immunoreactivity to the stress response protein ubiquitin was also induced by ischemia in a proportion of neurones. Both proteins are components of neurofibrillary tangles in Alzheimer's disease. Alterations of the microtubule-associated protein tau may be a feature of the early stages of the ischemia-induced degeneration and the ubiquitin response may be an attempt by compromised neurones to deal with the presence of abnormal proteins.
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PMID:Cerebral ischemia induces alterations in tau and ubiquitin proteins. 808 73

This report concerns an immunocytochemical and ultrastructural study of the motor cortices of 11 patients with amyotrophic lateral sclerosis (ALS). Specimens from 12 normal individuals served as controls. Antibodies against phosphorylated neurofilament (PNF; 200 kDa), ubiquitin, glial fibrillary acidic protein (GFAP) and phosphorylated tau protein were used. The pyramidal cells of layer III of all ALS patients were stained, with varying intensities, by the antibody to PNF. By contrast, Betz cells reacted less frequently with this antibody. Staining for GFAP was noted in numerous astrocytes in layer III and at the transition between white matter and motor cortex of most patients. Ubiquitin-positive inclusions were only occasionally seen in Betz cell and pyramidal cell of layer V. These observations indicate that alterations of the motor cortex occur first in the pyramidal cells of layer III rather than in Betz cells. Pyramidal cells and Betz cells were not stained by the antibody to phosphorylated tau protein. In controls, pyramidal cells and Betz cells were less frequently stained with the anti-neurofilament antibody than those from ALS patients. Immunoreactivity of GFAP in layer III and at the junction of white matter and motor cortex was observed in only one patient. Ultrastructural examination revealed that the Betz cells of some ALS patients had Bunina bodies (BB), Lewy body-like inclusions (LBI) and skein-like inclusions (SI), as well as bundles of filaments that were thicker than neurofilaments; some of these filaments appeared to be constricted. The incidence of these inclusions was lower than that seen in anterior horn neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunocytochemical and ultrastructural studies of the motor cortex in amyotrophic lateral sclerosis. 809 50

Alz-50 is a monoclonal antibody raised against ventral forebrain tissue from patients with Alzheimer's disease (AD). It was originally believed that the antigen recognized by Alz-50 was only found in degenerating neurons. However, recent studies indicate that Alz-50 stains neurons in a limited but specific distribution in normal brains throughout life. As the antigen recognized by Alz-50 in normal brains may give some insight into the AD degenerative process, we characterized Alz-50 staining in the normal ovine striatum using immunoblots and immunocytochemistry at the light and electron microscope levels. We then compared the Alz-50 staining pattern with those of NADPH diaphorase histochemistry and immunocytochemistry using antisera against several neuropeptides, Alzheimer-related proteins, and heat-shock proteins. Western blot analysis indicated that the epitope recognized by Alz-50 in the normal sheep brain is on the microtubule-associated protein tau, and preadsorbing Alz-50 with a peptide corresponding to the amino terminus of the tau molecule eliminated staining. Alz-50 labeled a single population of cells in the ovine striatum, the medium aspiny neurons. At the light microscope level, the granular staining pattern closely resembled Alz-50 immunoreactive neurons in the normal human striatum and in cells undergoing early degeneration in AD. Alz-50 immunoreactive neurons stained immunocytochemically with antisera against somatostatin, neuropeptide Y, and histochemically for NADPH diaphorase. These cells were morphologically characterized by smooth dendrites, elaborate local axonal plexuses, and indented nuclei with filamentous inclusions. Ultrastructurally, Alz-50 immunodecorated ribosomes and membranous structures (e.g. vesicles, endoplasmic reticulum), and many boutons which contained Alz-50-positive synaptic vesicles. None of the antisera against other Alzheimer-related proteins, including paired helical filament protein, ubiquitin, beta-amyloid protein, or heat-shock proteins specifically stained the population of cells labelled by Alz-50. Other tau antisera also did not specifically stain these cells. We conclude that Alz-50 recognizes an amino terminal epitope that is exposed on tau proteins within a single, discrete population of neurons in the normal sheep striatum. The presence of this epitope in a normal cell population raises the possibility that the early stages of AD degeneration may involve the activation of a normal cellular pathway that modifies the tau molecule.
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PMID:Alz-50 immunohistochemistry in the normal sheep striatum: a light and electron microscope study. 809 42

Characteristic changes appearing in the biopsied olfactory mucosa of Alzheimer's disease (AD) patients were investigated using immunohistochemical staining. Specimens were obtained from 6 patients who were clinically diagnosed with AD, 2 patients with cerebrovascular dementia and 5 age-matched patients with olfactory disturbance without dementia. In most AD cases, polyclonal tau protein immunoreactivity was seen in the dendrites, perikarya of the olfactory receptor cells in the olfactory epithelium and the olfactory nerve bundles in the lamina propria. In a few cases, tau protein immunoreactivity was found in the extracellular mass in the epithelium. Ubiquitin immunoreactivity was seen is the dendrites of olfactory receptor cells. On the other hand, in control cases, only dendrites and olfactory nerve bundles reacted to anti-polyclonal tau protein antiserum in a few cases. These results indicate that the neurofibrillary tangle-like tau protein immunoreactivity in the perikarya senile plaque-like extracellular mass and ubiquitin immunoreactivity in the olfactory epithelium were characteristic changes in AD, and olfactory mucosal biopsy is a useful method for the definitive diagnosis of AD.
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PMID:[Definitive diagnosis of Alzheimer's disease using olfactory mucosal biopsy]. 817 37

The major protein subunit of the paired helical filaments (PHF) of Alzheimer disease (AD) is the microtubule-associated protein tau. Tau is a family of phosphopolypeptides that are abnormally phosphorylated in PHF. In this study, a non-PHF pool of tau abnormally phosphorylated at Ser-199/202, and tau not phosphorylated at this site (AD P-tau and AD tau, respectively) were isolated from the 27,000 x g to 200,000 x g fraction of AD brain homogenate by extraction in 8 M urea, followed by dialysis against Tris buffer. AD P-tau and AD tau were further purified and separated from each other by acid precipitation, glial fibrillary acidic protein affinity chromatography, and phosphocellulose chromatography. The resulting AD P-tau and AD tau preparations were free of cytoskeletal proteins, ubiquitin, and beta-amyloid peptide. Immunochemical and morphological analysis of AD P-tau preparations revealed that most of the protein was of non-PHF origin. The AD P-tau was about 3-4-fold (approximately 8 mol P04/mol protein, M(r) 41,318) more phosphorylated than cytosolic tau from AD and control brains. Unlike PHF, the AD P-tau lacked ubiquitin. In AD brain the levels of cytosolic tau were about half of those in control aged cases. These findings suggest that the abnormal phosphorylation of tau in AD occurs in the cytosol.
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PMID:Microtubule-associated protein tau. Abnormal phosphorylation of a non-paired helical filament pool in Alzheimer disease. 822 87

Three cases of Lewy body disease were investigated in order to compare the morphological and immunohistochemical characteristics of the neuronal inclusions in the cerebral cortex (CC) and brain-stem (BS). Ultrastructurally, the CC contained intermediate-sized filaments with variable amounts of granular material and other organelles, whereas the BS consisted of an electron-dense core and an outer area with radially oriented filaments. The cerebral cortex was immuno-reactive with antibodies against tyrosine hydroxylase (TH) and tau protein, and differed from BS. In addition, although the CC were antigenically similar to BS in their neurofilament (70, 160 and 200 kDa) and ubiquitin contents, the localization of neurofilament immunoreactivity differed between them, being confined positively to the core of CC, but to the periphery of the BS. Although Lewy bodies (LB) in idiopathic Parkinson's disease are morphologically similar to BS, they have been reported to differ in their immunoreactivity with antibodies against tau. It has been reported that CC differ from LB with regard to immunoreactivity with antibodies against TH and tropomyosin. It is inferred that these inclusions (CC, BS and LB) differ in morphogenesis.
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PMID:Immunohistochemistry of neuronal inclusions in the cerebral cortex and brain-stem in Lewy body disease. 829 42

We immunostained muscle biopsies of 8 patients with sporadic inclusion body myositis (S-IBM), 7 patients with autosomal recessive hereditary inclusion body myopathy (H-IBM) (both diseases being characterized by similar muscle fiber vacuoles containing inclusions), and 11 normal and disease controls. We used the following well-characterized antibodies against tau protein: Tau-1, Alz-50, and anti-paired helical filament (PHF) antiserum. By light microscopy, in all S-IBM muscle biopsies virtually all vacuoles immunoreactive for ubiquitin and beta-amyloid protein also contained inclusions immunoreactive with Alz-50 and anti-PHF antiserum. With tau-1 antibody, strong immunoreactivity in the vacuoles was obtained only after dephosphorylation of muscle sections. By electronmicroscopy, all three antibodies immunodecorated exclusively cytoplasmic twisted tubulofilaments (TTFs). In H-IBM, virtually all ubiquitin and beta-amyloid-positive muscle fiber vacuoles contained inclusions immunoreactive with anti-PHF antiserum, but in only 40% of those fibers were the inclusions immunoreactive with Alz-50. In six H-IBM patients there were no tau-1 immunoreactive inclusions in any of their vacuolated muscle fibers; in one patient, 24% of the vacuolated fibers had tau-1 immunoreactivity. By demonstrating that hyperphosphorylated tau, which is characteristic of Alzheimer brain PHFs, is a component of S-IBM-muscle TTFs (which are also ultrastructurally similar to PHFs), our study: 1) provides the first demonstration of abnormally accumulated tau in nonneural tissue and 2) suggests that the cytopathogenesis in Alzheimer brain and S-IBM muscle may share some similar mechanisms. Whether the difference in tau immunoreactivity between S-IBM and most of the H-IBM patients reflects a difference in genetically determined transcriptional or posttranslational modifications of tau protein or other factors remains to be determined.
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PMID:Twisted tubulofilaments of inclusion body myositis muscle resemble paired helical filaments of Alzheimer brain and contain hyperphosphorylated tau. 829 7


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