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)

Neurofibrillary tangles are described in Guamanian and post-encephalitic forms of motor neuron disease (MND) but not in sporadic MND. We report the neuropathological findings in a 79-year-old man who died after a 1-year history of MND without extrapyramidal features or dementia. There was no family history of neurological disease and he had not visited Guam. The spinal cord showed loss of anterior horn cells, and skeletal muscle typical changes of denervation. The brain appeared macroscopically normal but histology revealed many neurofibrillary tangles, particularly in medial temporal lobe structures, insula, nucleus basalis, hippocampus, oculomotor nucleus, raphe nuclei and locus ceruleus. Neurofibrillary tangles were not seen in the primary motor cortex, which appeared histologically unremarkable. Occasional tangles were present in the substantia nigra and pontine nuclei. None were seen in the cerebellum, medulla or spinal cord. The tangles were argyrophilic, and, in sections stained with thioflavin-S, both the intracellular and the extracellular tangles fluoresced strongly under ultraviolet light. The intracellular neurofibrillary tangles reacted strongly with an antibody to tau protein, and only occasional tangles showed weak ubiquitin immunoreactivity. Scattered neuropil threads were present in the cortex in the areas of neurofibrillary tangle formation. No plaques were present in any part of the brain and no A4/beta protein immunoreactivity was detected. Ultrastructural examination revealed Alzheimer-type neurofibrillary tangles composed of paired helical filaments. The present findings further extend the spectrum of diverse neurological disorders associated with neurofibrillary tangles.
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PMID:Motor neuron disease with neurofibrillary tangles in a non-Guamanian patient. 757 72

We examined a 65-year-old patient with clinicopathological features that met the criteria of frontotemporal dementia (FTD), particularly frontal lobe degeneration (FLD). He came from a family with concentrated occurrence of dementia symptoms in the presenium. Neuropathological examination disclosed brain atrophy locally pronounced on the frontotemporal lobes with characteristic neuronal loss, microvacuolation and astrocytic gliosis. There were no pathological hallmarks such as senile plaques, Pick bodies (PBs), achromatic cells and neurofibrillary tangles. Precise separation of FTD from Pick disease (PD) and motor neuron disease with dementia (MNDD) has not yet been established, and they are included in one spectrum. Antibodies against paired helical filament tau protein demonstrated immunopositive cytoskeletal structures within the neurons as well as the glial cells in the brain of the present case. They were selectively stained with tau 199/202 but not tau 396, which were provided newly to recognize phosphorylation at Ser 199/202 or Ser 396 in tau, respectively. We investigated tau pathology in the present case in comparison to 8 cases with PD that were clinicopathologically confirmed. Neither tau 199/202 nor tau 396 stained the CNS structures in PD cases with few PBs, while both stained evidently those as well as PBs in PD cases associated with many PBs; so that the present case could be distinguished from PD on the basis of the immunoreactivity to site-specific phosphorylated tau. Our result suggests that FTD, especially familial FLD type might involve unique tau pathology, no matter whether FLD is a distinct entity from PD, or a variant form in the wide FTD spectrum including PD and MNDD and other related disorders.
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PMID:Selective expression of Ser 199/202 phosphorylated tau in a case of frontotemporal dementia. 952 99

Microtubule-associated protein tau forms neurofibrillary lesions in Alzheimer's disease and several other neurodegenerative disorders, such as Niemann-Pick disease type C, subacute sclerosing panencephalitis, argyrophilic grain disease, myotonic dystrophy and motor neuron disease with neurofibrillary tangles. In this study we have compared the characteristics of tau pathology in these diseases using immunohistochemistry and phosphorylation-dependent and phosphorylation-independent anti-tau antibodies. The pattern of staining for heparan sulphate and alpha-synuclein was also investigated. We show that in all of these diseases tau deposits were stained by all anti-tau antibodies used, with the exception of argyrophilic grains which do not stain with antibody 12E8, confirming our previous findings. Heparan sulphate staining was present to a variable extent in all of these diseases, with the exception of subacute sclerosing panencephalitis, in which no staining was observed. Heparan sulphate staining coexisted with tau staining. In some cases it was more extensive than the tau staining. Alpha-synuclein staining was present in presynaptic terminals with the exception of one case of Alzheimer's disease, in which alpha-synuclein-positive Lewy bodies were observed in the hippocampal formation. These findings indicate that tau deposits are antigenically similar in several neurodegenerative diseases and that tau staining is often associated with heparan sulphate staining, supporting the concept that heparan sulphate may be involved in the assembly of tau protein into filaments.
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PMID:Microtubule-associated protein tau, heparan sulphate and alpha-synuclein in several neurodegenerative diseases with dementia. 1037 77

We have studied Gallyas- and tau-positive glial structures in three autopsied cases of motor neuron disease with dementia (MND-D). Gallyas-positive, tau-immunoreactive thread-like structures in the neuropil and crescent/coiled inclusions in the glial cells were mainly observed in the hippocampus, parahippocampal gyrus, and amygdaloid nucleus. Double staining using Gallyas staining and carbonic anhydrase 2 (CA2) immunohistochemistry revealed that some crescent/coiled inclusions occurred in the CA2-immunopositive cytoplasm of the oligodendroglia. Electron microscopic study with the Gallyas-Braak method revealed that the inclusion was a reticular, partly compact mass, containing 15 nm fibrils around round or oval nuclei. Since the regions where these structures appeared exhibited neuronal loss with gliosis, these data suggest that a cytoskeletal abnormality involving tau protein in glia might be associated with the degenerative process of MND-D.
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PMID:Gallyas- and tau-positive glial structures in motor neuron disease with dementia. 1050 30

Frontotemporal lobar degeneration is the second most common form of cortical dementia in the presenium after Alzheimer's disease. Clinically, based on consensus guidelines, three distinct disease entities can be distinguished: frontotemporal dementia, semantic dementia and progressive nonfluent aphasia. Dementia of frontal type and motor neuron disease inclusion dementia are the most frequent neuropathological subtypes of frontotemporal lobar degeneration. By using immunohistochemistry, the latter is characterized by the presence of filamentous ubiquitin-reactive but tau-negative inclusions in nerve cell bodies and neurites. In contrast, Pick's disease and familial frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) are both characterized by abundant filamentous nerve cell inclusions made up of the microtubule-associated protein tau. The recent discovery of more than 15 different mutations in the tau gene in FTDP-17 brought the tau protein to the centre stage. These findings had a major impact on our understanding of neurodegenerative disorders characterized by tau filamentous inclusions in neurones and/or glial cells which are grouped under the generic term of tauopathies. However, as exciting these new molecular insights are, it would be inappropriate to lump frontotemporal lobar degeneration as tauopathies. Recent neuropathological and genetic data strongly suggest that there is more than one genetic background for frontotemporal lobar degeneration.
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PMID:Frontotemporal lobar degeneration. An update on clinical, pathological and genetic findings. 1124 85

The syndrome of frontotemporal dementia represents a diverse group of diseases presenting with behavioral and cognitive disturbances. The expression of the microtubule-associated protein tau was studied in postmortem samples of frontal cortex of 19 cases (12 Pick's disease A, B, C; 4 dementia lacking distinct histology; 3 motor neuron disease type) by Western blotting with a phosphorylation-independent anti-tau antibody. The presence of tau protein was detected in all cases evaluated, including the 11 brains classified as frontotemporal lobe degeneration (diagnostic categories Pick's disease B, C and dementia lacking distinct histology). These findings indicate that the recently reported decreased expression of tau protein in frontotemporal lobe degeneration represents pathogenic mechanism of neurodegeneration detectable only in a special subset of these disorders.
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PMID:Tau protein expression in frontotemporal dementias. 1171 Dec 5

The calcium-activated protease calpain cleaves a variety of biologically important proteins and serves, therefore, as a key regulator of many cellular functions. Activation of both main isoforms, calpain 1 and calpain 2, was demonstrated previously in Alzheimer's disease. In this report, antibodies specifically recognizing the active form of calpain 2 were used to investigate calpain 2 activation in a broad range of neurodegenerative diseases, utilizing multiple-label confocal immunofluorescence imaging. With rare exceptions, the active form of calpain 2 was found in colocalization with hyperphosphorylated tau protein. Aggregates of mutated huntingtin, alpha-synuclein, or unidentified protein in motor neuron disease type of frontotemporal dementia were always negative. These findings indicate that calpain 2 activation is not a general response to protein aggregation. In tauopathies, more pathological inclusions were labeled for hyperphosphorylated tau than for activated calpain 2. The extent of colocalization varied in both a disease-specific and cell-type specific manner. The active form of calpain 2 was detected in 50-75% of tau neurofibrillary pathology in Alzheimer's disease, Alzheimer neurofibrillary changes and Down's syndrome, as well as in the accompanying Alzheimer-type tau pathology in diffuse Lewy bodies disease, progressive supranuclear palsy, and corticobasal degeneration. For glial cells, only 10-25% of tuft-shaped astrocytes, glial plaques, or coiled bodies contained activated calpain 2. The majority of Pick bodies were negative. The association of calpain 2 activation with hyperphosphorylated tau might be the result of an attempt by the calpain proteolytic system to degrade the tau protein aggregates. Alternatively, calpain 2 could be directly involved in tau hyperphosphorylation by modulating protein kinase activities. Overall, these results provide evidence of the important role of the calpain proteolytic system in the pathogenesis of neurodegenerative diseases with tau neurofibrillary pathology.
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PMID:Calpain activation in neurodegenerative diseases: confocal immunofluorescence study with antibodies specifically recognizing the active form of calpain 2. 1207 Jun 70

Recent work on frontotemporal dementia (FTD) has revealed the existence of at least 3 genetically distinct groups of inherited FTD: FTDP-17, FTD and motor neuron disease linked to chromosome 9, and FTD linked to chromosome 3 (FTD-3). Tau, on chromosome 17, is the only gene where mutations have been identified and its involvement in FTD has been firmly established. The genes on chromosome 9 and chromosome 3 associated with familial forms of FTD remain to be identified. Abnormal aggregates of tau protein characterize the brain lesions of FTDP-17 patients and ubiquitin inclusions have been found in FTD with motor neuron disease linked to chromosome 9. In this study the frontal cortices of 3 FTD-3 patients from a unique Danish family were examined for characteristic neuropathological features. In these brains tau inclusions were present in neurons and some glial cells in the absence of beta-amyloid deposits. The presence of filamentous tau protein in the frontal cortex of these patients suggests a possible link between tau and the genetic defect present on chromosome 3 and associated with FTD-3, although the limited amount of tau deposits observed makes it difficult to define this as a tauopathy.
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PMID:Tau protein in frontotemporal dementia linked to chromosome 3 (FTD-3). 1450 43

We describe the brain autopsy findings from three of five siblings who suffered dementia with clinical diagnoses including Alzheimer's, Parkinson's, and Pick's disease. Five other living siblings appear unaffected. All of the autopsied brains showed severe atrophy (brain weights 613, 641, and 750 g) of the frontal and temporal lobes, and to a slightly lesser extent of the parietal lobes, while the occipital lobes were relatively preserved. The substantia nigra showed marked neuronal loss with gliosis. No ballooned neurons, neurofibrillary tangles, neuritic plaques, Pick bodies, or Lewy bodies were found in these brains. Immunohistochemistry for tau protein failed to reveal neuronal or glial inclusions, and normal tau protein was found in a separate Western blot study [Adamec et al. (2001) Neurosci Lett 315:21-24]. Rare neurons with ubiquitinated cytoplasmic inclusions were scattered in the neocortex and hippocampus. The overall pathological features were consistent with a severe form of frontotemporal dementia (FTD) with involvement of the substantia nigra. Whether the rare ubiquitinated inclusions are sufficient to classify these cases as FTD with motor neuron disease type inclusions but without motor neuron disease, or FTD dementia lacking distinctive histological features remains unclear. The features of lobar circumscribed atrophy without Pick bodies and without ballooned neurons, however, are consistent with Pick disease group C in the Constantinidis classification [Constantinidis et al. (1974) Eur Neurol 11:208-217].
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PMID:Familial frontotemporal dementia: a report of three cases of severe cerebral atrophy with rare inclusions that are negative for tau and synuclein, but positive for ubiquitin. 1510 11

The frontotemporal dementias (FTDs) are a heterogeneous group of neurodegenerative disorders that are characterized clinically by dementia, personality changes, language impairment, and occasionally extrapyramidal movement disorders. Historically, the diagnosis and classification of FTDs has been fraught with difficulties, especially with regard to establishing a consensus on the neuropathologic diagnosis. Recently, an international group of scientists participated in a consensus conference to develop such neuropathologic criteria. They recommended a diagnostic classification scheme that incorporated a biochemical analysis of the insoluble tau isoform composition, as well as ubiquitin immunohistochemistry. The use and reliability of this classification system has yet to be examined. In this study, we evaluated 21 cases of FTD. Using traditional histochemical stains and tau protein and ubiquitin immunohistochemistry, we separated each case into one of the following categories: classic Pick disease (PiD; n = 7), corticobasal degeneration (CBD; n = 5), dementia lacking distinctive histopathologic features (DLDH; n = 4), progressive supranuclear palsy (PSP; n = 2), frontotemporal lobar degeneration with motor neuron disease or motor neuron disease-type inclusions (FTLD-MND/MNI; n = 2), and neurofibrillary tangle dementia (NFTD; n = 1). Additionally, we independently categorized each case by the insoluble tau isoform pattern, including 3R (n = 5), 4R (n = 7), 3R/4R (n = 3), and no insoluble tau (n = 6). As suggested by the proposed diagnostic scheme, we found that the insoluble tau isoform patterns correlated strongly with the independently derived histopathologic diagnoses (p < 0.001). The data show that cases containing predominantly 3R tau were classic PiD (100%). Cases with predominantly 4R tau were either CBD (71%) or PSP (29%). Cases with both 3R and 4R tau were either a combination of PiD and Alzheimer disease (67%) or NFTD (33%). Finally, cases with no insoluble tau were either DLDH (67%) or FTLD-MND/MNI (33%). To further characterize these cases, we also performed quantitative Western blots for soluble tau, APOE genotyping, and, in selected cases, tau gene sequencing. We show that soluble tau is reduced in DLDH and FTLD-MND/MNI and that APOE4 is overrepresented in PiD and DLDH. We also identified a new family with the R406W mutation and pathology consistent with NFTD. This study validates the recently proposed diagnostic criteria and forms a framework for further refinement of this classification scheme.
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PMID:Neuropathologic, biochemical, and molecular characterization of the frontotemporal dementias. 1589


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