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)

Frontotemporal dementia (FTD) is a common neurodegenerative disorder and is connected with about 10% of all dementias. In approximately half of all FTD cases, a positive family history has been reported. To date, several mutations at the tau protein gene (MAPT) were identified causing familial and sporadic FTD. Extensive polymorphic variability at the MAPT gene has also been shown to be a risk factor in progressive supranuclear palsy (PSP). The recently described gene Saitohin (STH), located in the intron 9 of MAPT gene, was also reported to be polymorphic. In the present study 23 unrelated Polish patients with clinically defined sporadic and familial FTD were screened for mutations at the MAPT gene. No pathogenic mutations were found in the group. Several novel silent intronic and exonic mutations were identified, most of them associated with two common haplotypes. In the reported group no correlation between extended MAPT haplotype and APOE genotype was determined. There was also no observed relation between age of onset and APOE status. At the STH gene only a common polymorphic change was found. It is postulated that MAPT mutations are not connected with most of the FTD cases in the Polish population.
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PMID:Mutation screening of the MAPT and STH genes in Polish patients with clinically diagnosed frontotemporal dementia. 1282 37

Abundant neurofibrillary lesions made of abnormal and hyperphosphorylated microtubule-associated protein tau constitute one of the defining neuropathological features of Alzheimer's disease. However, tau containing filamentous deposits in neurons and/or glial cells also define a heterogeneous group of neurodegenerative disorders clinically characterized by dementia and/or motor syndromes. Thus, all these disorders are collectively grouped under the generic term of tauopathies. In the present review we outline the morphological and biochemical characteristics of some major tauopathies, including Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration and argyrophilic grain disease. The second part will deal with the recent discovery of tau gene mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 which demonstrates that tau dysfunction can lead to neurodegeneration. Finally, we will discuss the very recent finding of 'tau-deficient' tauopathy in a subset of frontotemporal dementia cases.
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PMID:The neuropathological spectrum of neurodegenerative tauopathies. 1293 31

Several distinct clinical syndromes presenting with parkinsonism have been associated with subcortical neurofibrillary degeneration and the abnormal accumulation of hyperphosphorylated tau protein in the brain. Mutations of tau have been linked with a small number of autosomal dominantly inherited families who present with frontolimbic cognitive deficits, behavioural disorders, and Parkinson's syndrome. Some of the sporadic disorders (progressive supranuclear palsy [PSP] and corticobasal degeneration) have been referred to by molecular pathologists as primary tauopathies, implicating abnormalities of tau in their pathogenesis. We have identified a sporadic parkinsonian syndrome characterised by bradykinesia, a variable response to levodopa, and a mean duration of disease of 9 years, which resembles bodig (Parkinson's-dementia of Guam), and histologically has close similarities with both PSP and postencephalitic parkinsonism. Further characterisation of these cases frequently confused with Parkinson's disease may broaden the clinical spectrum of parkinsonian disorders linked with neurofibrillary tangle formation.
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PMID:Parkinson's syndrome associated with neurofibrillary degeneration and tau pathologic findings. 1450 53

Argyrophilic grain disease (AgD) is a four-repeat tauopathy that is almost exclusively restricted to allocortical areas. Progressive supranuclear palsy and corticobasal degeneration also show predominant deposition of four-repeat tau filaments, and are associated with the tau H1 haplotype. We investigated a possible association between AgD and the tau H1 haplotype. In AgD, no difference between the prevalence of the tau H1 haplotype or H1/H1 genotype was observed when compared to non-demented control cases. These data suggest that a dysfunction of the tau protein in AgD-in contrast to other four-repeat tauopathies-may arise irrespective of the genetic background regarding the tau H1 or H2 haplotypes.
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PMID:Argyrophilic grain disease: molecular genetic difference to other four-repeat tauopathies. 1451 64

We found previously that aggregated insoluble tau protein in progressive supranuclear palsy (PSP) brains exhibits a heterogeneous pattern that is not segregated by the type of clinical presentation. Here we have investigated tau isoform composition from 20 PSP cases and found marked variation between different brains. Cases were classified into three groups, each comprising essentially of (1) 1N4R; (2) 1N4R and 1N3R; or (3) 1N4R, 1N3R and 0N4R tau isoforms. There was also an absence of a simple relationship between isoform composition and the pattern of insoluble tau before dephosphorylation. We conclude that there is distinct molecular heterogeneity in the involvement of tau isoforms in the tau pathology in PSP.
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PMID:Differential involvement and heterogeneous phosphorylation of tau isoforms in progressive supranuclear palsy. 1496 40

Tau protein is the major component of the intracellular filamentous deposits that define a number of neurodegenerative diseases. They include the largely sporadic Alzheimer's disease, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Pick's disease (PiD), argyrophilic grain disease, as well as the inherited frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). The identification of mutations in Tau as the cause of FTDP-17 established that dysfunction or misregulation of tau protein is sufficient to cause neurodegeneration and dementia. At an experimental level, the new understanding is leading to the development of good transgenic animal models of the tauopathies.
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PMID:Tau protein and neurodegeneration. 1503 6

Progressive supranuclear palsy is a neurodegenerative disorder accompanied by parkinsonism, disturbances of eye movements, pseudobulbar palsy and often cognitive decline. Onset of disease is usually between 50-70 years of age and mean survival is 5-8 years. The prevalence of PSP has been estimated at around 5 per 100,000, although exact figures for the population of the Netherlands are not yet available. International consensus criteria differentiate between possible, probable and definite PSP; the latter requiring neuropathological confirmation. An extensive differential diagnosis may be made early in the course of the disease, but at a later stage development of the characteristic symptoms will make diagnosis easier. Imaging techniques can lend support to the clinical diagnosis to a limited extent, although they lack sufficient specificity to confirm it. PSP is a 'tauopathy' characterized by aggregates of abnormal tau protein in the basal ganglia and brainstem. Some mutations in the tau gene can cause a clinical and pathological picture similar to that of PSP, although most patients with sporadic and familial PSP do not have tau mutations. Various studies have found a strong association between PSP and a specific tau haplotype (H1 haplotype), but its role in the pathophysiological mechanism of PSP is still unclear and needs further research.
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PMID:[Progressive supranuclear palsy; an unusual form of parkinsonism]. 1505 50

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are sporadic neurodegenerative diseases presenting as atypical parkinsonian disorders, characterized by the presence of tau-positive neurofibrillary tangles. Recently, an extended haplotype (H1E) of 787.6 kb that comprises several genes including MAPT showed increased association with PSP. The objective of this study was to determine the size of the H1E haplotype associated with PSP and CBD in different populations and to identify specific subhaplotypes in the background of H1E haplotype. Nineteen single nucleotide polymorphisms (SNPs) in the 17q21 region were genotyped in two case-control samples. The SNPs that were associated with higher risk for the disease in the homozygous state delimit a region of more that 1 Mb. Haplotype analyses in the Spanish sample showed that the most frequent haplotype found among the patients (H1E'), which extends 1.04 Mb and contains several genes such as MAPT, CRHR1, IMP5, Saitohin, WTN3, and NSF. A specific subhaplotype (H1E'A) was present in 16% of PSP patients but was not observed in the controls. Furthermore, the H2E'A haplotype, was rarely present in the disease group suggesting that it plays a protective role. The identification of these specific subhaplotypes that modify risk for PSP/CBD supports the hypothesis that a pathogenic allele exists in a subgroup of PSP patients.
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PMID:Novel haplotypes in 17q21 are associated with progressive supranuclear palsy. 1529 77

The MAPT H1 haplotype has been associated with four-repeat (4R) tauopathies, including progressive supranuclear palsy, corticobasal degeneration, and argyrophilic grain disease. More controversial is that the same haplotype has been associated with Parkinson disease (PD). Using H1-specific single-nucleotide polymorphisms, we demonstrate that MAPT H1 is a misnomer and consists of a family of recombining H1 alleles. Population genetics, linkage disequilibrium, and association analyses have shown that specific MAPT H1 subhaplotypes are preferentially associated with Parkinson disease. Using a sliding scale of MAPT H1-specific haplotypes--in age/sex-matched PD cases and controls from central Norway--we have refined the disease association to within an approximately 90-kb interval of the 5' end of the MAPT locus.
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PMID:Linkage disequilibrium and association of MAPT H1 in Parkinson disease. 1529 35

The deposition of abnormal levels of tau protein is a major neuropathological feature of progressive supranuclear palsy (PSP), and the presence of tuft-shaped astrocytes is a neuropathological hallmark of PSP. We examined the topographic distribution of tuft-shaped astrocytes in the cerebral hemisphere by Gallyas-Braak silver staining in three Japanese autopsy cases of typical PSP. The distribution of tuft-shaped astrocytes was relatively uniform between cases. Tuft-shaped astrocytes were identified predominantly in posterior frontal areas such as the precentral gyrus and premotor and supplementary motor areas (Brodmann areas 4, 6 and 8). Tuft-shaped astrocytes were most dense in areas of cortical convexity, and they were more abundant in the crests of the cerebral gyri than in the valleys of the cerebral sulci. The temporal, parietal and occipital cortices, including the hippocampal formation and cingulate gyrus, were relatively free of tuft-shaped astrocytes. We confirmed involvement of the cerebral cortex in the pathology of PSP, and showed the widespread presence of tuft-shaped astrocytes, particularly in the precentral gyrus and premotor and supplementary motor areas, to be an essential neuropathological feature of PSP. The extra-pyramidal and pyramidal signs, supranuclear oculomotor abnormalities and other cortical signs associated with PSP may be related to the high density of tuft-shaped astrocytes in the precentral gyrus and premotor and supplementary motor areas. Dementia, apraxia, aphasia and frontal lobe signs may also result, at least in part, from this cortical involvement.
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PMID:Distribution of tuft-shaped astrocytes in the cerebral cortex in progressive supranuclear palsy. 1536 23


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