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)

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

The microtubule-associated phosphoprotein, tau, is an integral component of paired helical filaments in Alzheimer neurofibrillary tangles (NFT). The mechanism of NFT formation is unknown but aberrant phosphorylation of tau may be contributory. Calcium/calmodulin-dependent protein kinase type II (CaM kinase II), the most abundant kinase in the brain, phosphorylates tau in vitro. We found CaM kinase II immunoreactivity concentrated in human hippocampal pyramidal neurons of CA1 and the subiculum. In Alzheimer's disease (AD) staining intensity of CA1 and subicular neurons is strikingly increased despite NFT formation and neuronal depletion. Enhanced CaM kinase II activity, possibly a result of deafferentation, may contribute to phosphorylation of tau protein leading to NFT deposition and neuronal death in AD.
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PMID:Hippocampal neurons predisposed to neurofibrillary tangle formation are enriched in type II calcium/calmodulin-dependent protein kinase. 215 60

Microtubule-associated protein tau is abnormally hyperphosphorylated in the brain of patients with Alzheimer disease (AD). Previous studies have shown (i) that in vitro tau can be phosphorylated to an Alzheimer abnormally phosphorylated state-like protein by proline-directed protein kinases MAP kinase and p34cdc2, and (ii) that the AD abnormally phosphorylated tau can be in vitro dephosphorylated by protein phosphatases PP-2B, PP-2A and PP-1 and not by PP-2C. However, to have a direct effect on the regulation of phosphorylation of tau, these enzymes should be present in the affected neurons. In the present study immunocytochemical localization of protein phosphatases PP-1, PP-2A, PP-2B and PTP, and protein kinases MAP kinase and p34cdc2 were studied in the hippocampal formation of AD and as a control in non-demented elderly patients. All the protein phosphatases and protein kinases studied were localized to both granular and pyramidal neurons. In the pyramidal neurons, the enzymes staining was observed in neuronal soma and neurites. PTP-1B, PP-1 and PP-2A were also highly expressed in microglia. The topographical distributions of all the enzymes studied were similar, i.e. the intensity of immunostaining in hippocampus in end-plate (CA3 and CA4) > prosubiculum, subiculum > entorhinal cortex > dentate gyrus > CA2 > CA1. Furthermore, the expression of all the enzymes was also observed in the tangle-bearing neurons. The PP-2B staining of the tangle-bearing neurons was weaker than the unaffected neurons in the same tissue section field in AD cases.
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PMID:Expression of protein phosphatases (PP-1, PP-2A, PP-2B and PTP-1B) and protein kinases (MAP kinase and P34cdc2) in the hippocampus of patients with Alzheimer disease and normal aged individuals. 781 92

One unique phosphorylation site consistently found in paired helical filament tau, serine 413, is modified by tau protein kinase I/glycogen synthase kinase-3 beta but no other known tau kinase. Here we present immunocytochemistry from Alzheimer's disease brains showing that focal subpopulations of hippocampal CA1 pyramidal neurons and neuritic plaques are strongly reactive for tau protein kinase I/glycogen synthase kinase-3 beta and tau phosphoserine 413 in early stages of pathology. Colocalization of these epitopes suggests that tau protein kinase I/glycogen synthase kinase-3 beta abnormally phosphorylates tau and is in a position to disrupt neuronal metabolism in anatomical areas vulnerable to Alzheimer's disease.
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PMID:Immunocytochemistry of tau phosphoserine 413 and tau protein kinase I in Alzheimer pathology. 893 Mar 58

In the course of Alzheimer's disease, specific CA1 pyramidal cells develop dendritic changes, which can only be observed transiently. Distal segments of the apical dendrite running through the stratum lacunosum-moleculare show spindle-shaped dilations filled with abnormal tau protein. The alteration eventually leads to amputation of the changed segment. The damage first appears at stage II in the evolution of the neurofibrillary changes [5], is best developed at stage III, and vanishes from the tissue at stage IV. It is usually not observed in stages V and VI (fully developed Alzheimer's disease).
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PMID:Alzheimer's disease: transiently developing dendritic changes in pyramidal cells of sector CA1 of the Ammon's horn. 911 96

Argyrophilic grains (ArG) and coiled bodies of argyrophilic grain disease (AgD) and the neurofibrillary lesions of Alzheimer's disease (AD) share similar antigenic determinants, among them hyperphosphorylated microtubule-associated protein tau. Nothing is known about the mechanisms underlying tau hyperphosphorylation in AgD, the hyperphosphorylated sites or the intracellular distribution of abnormally phosphorylated tau. We have analysed brain tissue sections from 41 subjects with AgD with a panel of phosphorylation-dependent (AT270, AT8, Tau-1, AT180, 12E8, PHF-1 and AT100) and phosphorylation-independent anti-tau antibodies (N-tau 5, 304, 189 and 134). All antibodies labelled ArG, coiled bodies and neurofibrillary lesions, with the exception of antibody 12E8, which stained a subset of neurofibrillary tangles, but no ArG or coiled bodies. Most pyramidal neurons in areas rich in ArG showed diffuse granular tau labelling in cell bodies and dendrites. Only very few tau-positive cells also contained neurofibrillary tangles. Phosphorylation-dependent anti-tau antibodies also stained a felt-like network of Gallyas-negative filiform neurites in layer CA1 of the hippocampus and in layer pre-B of the transentorhinal cortex. These results demonstrate a widespread hyperphosphorylation of tau protein in the somatodendritic domain of neurons in AgD, in addition to silver grains in the neuropil. Unlike in AD, tau hyperphosphorylation in the somatodendritic domain in AgD does not appear to be followed by neurofibrillary tangle formation, even in the presence of widespread ArG in the neuropil. Furthermore, our data suggest that no strict correlation exists between the presence or density of ArG in the limbic area and the occurrence of dementia.
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PMID:Argyrophilic grain disease: widespread hyperphosphorylation of tau protein in limbic neurons. 914 86

We report the presence of round eosinophilic intranuclear inclusions in a patient with sporadic amyotrophic lateral sclerosis (ALS). The inclusions were limited to the hippocampal pyramidal neurons; they were frequently encountered in the CA1 and CA2 regions and much less frequently in the CA3 and CA4 regions and in the subiculum. Ultrastructurally, they consisted of randomly oriented straight filaments, each about 8-14 nm in diameter, some of which had a tubular appearance in cross-section. Electron-dense, granular material was intermingled with the filaments. Immunohistochemically, all the inclusions were positive for ubiquitin, but were negative for several kinds of cytoskeletal protein, including actin, glial fibrillary acidic protein, vimentin, neurofilament polypeptides, keratin, tubulin, tau protein and microtubule-associated protein 2. To our knowledge, this type of neuronal intranuclear inclusion has not so far been reported in ALS, and its distribution limited to the hippocampal formation is of great interest.
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PMID:Eosinophilic intranuclear inclusions in the hippocampal pyramidal neurons of a patient with amyotrophic lateral sclerosis. 993 Sep 2

Nitric oxide is a multifunctional molecule that acts as messenger/modulator in synaptogenesis and potential neurotoxin and is synthesized by three isozymes of Nitric oxide synthase (NOS). The role of NOS in Alzheimer's disease (AD) is unclear. For example, neurons in the entorhinal cortex (EC) that are highly vulnerable to neurodegeneration in AD express low levels of NOS and while it has been suggested that the inducible form of NOS is upregulated in AD, it is still not clear if the constitutive expressed isozyme (nNOS) is involved in the process of neurodegeneration. In order to better understand the role of nNOS in the pathogenesis of AD, sections from the EC and hippocampus (HC) of AD and control cases were immunohistochemically analyzed by single- and double-immunolabeling using antibodies against nNOS and PHF-tau. Semiquantitative assessment of numbers of nNOS expressing neurons in different areas of the HC and EC showed a remarkable loss of nNOS expressing neurons in the entorhinal cortex layer II and--less severe--CA1 and CA3 of the hippocampus in patients with AD. In addition, double-immunolabeling studies revealed that nNOS is strongly associated with neurofibrillary tangles and plaques. These findings indicate that nNOS expressing neurons are highly susceptible to neurodegeneration and that nNOS might contribute to the pathogenesis of AD.
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PMID:nNOS expressing neurons in the entorhinal cortex and hippocampus are affected in patients with Alzheimer's disease. 951 29

Braak's argyrophilic grains (ArGs) are spindle-shaped neuropil structures originally found in patients afflicted with adult onset dementia. We recently observed that tau protein is hyperphosphorylated in most nerve cells in areas rich in ArGs, suggesting that these grains may be a morphological expression of tau protein pathology in local neurons. The aim of this study was therefore to determine in three cases with ArGs whether grains are associated with individual neurons containing hyperphosphorylated tau. A combination of Gallyas silver staining and AT8 immunocytochemistry was used. AT8 is a monoclonal antibody that recognizes tau in a phosphorylation-dependent manner. Up to 80% of pyramidal cells of sector CA1 showed diffuse AT8 staining of their cell bodies and dendrites. Most grains were freely scattered throughout the neuropil. However, some were clearly located in side-branches of apical dendrites of AT8 immunoreactive pyramidal neurons. Dendritic branches often formed bush-like ramifications containing clusters of ArGs. Other dendrites consisted of a single stump containing one or two large grains at their tips. Spheroidal enlargements of dendritic branches, with a size corresponding to ArGs, were also found in Golgi Cox preparations of cases with ArGs but not in Alzheimer's disease cases or in controls. Our results show that some ArGs are formed within dendrites of neurons whose most obvious pathology is a diffuse hyperphosphorylation of the tau protein. Furthermore, morphology of dendrites containing grains suggests that a process of progressive shrinkage of dendrites is taking place in neurons bearing ArGs.
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PMID:Argyrophilic grains of Braak: occurrence in dendrites of neurons containing hyperphosphorylated tau protein. 954 29

A study of brains of 16 dogs from one to 19 years of age showed a structure- and cell-type- specific pattern of tau protein phosphorylation at mAb Tau-1 site and the absence of phosphorylation at the mAb AT8 site. Strong immunolabeling with mAb Tau-1 of the mossy fibers and perikarya of neurons in sectors CA3 and CA4 of the cornu Ammonis, less intensive staining in the cytoplasm in neocortical and subcortical neurons, and selective staining of some pyramidal cells in sectors CA1 and CA2 show differences in the amount of phosphorylated tau, not only in different types of neurons, but also in different parts of the cell. The immunoreactivity of oligodendrocytes and the absence of the reaction in astrocytes reflect differences in tau phosphorylation in glial cells. Marked immunoreactivity in 13 dogs but minimal reaction in brains of three other dogs appears to reflect interindividual differences, which are associated presumably with genetic background. Shrinkage of neurons, tortuosity of mossy fibers, accumulation of phosphorylated tau in the nucleoplasm, and deformation of the nuclei of neurons and oligodendrocytes suggest that excessive phosphorylation at the mAb Tau-1 site is associated with neuronal and oligodendrocyte degeneration and, possibly, cell death.
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PMID:Region- and cell-type-specific pattern of tau phosphorylation in dog brain. 974 20


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