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)

In order to improve diagnosis of Alzheimer's disease (AD), candidate biological markers in CSF as well as structural and functional imaging were investigated. Biomarkers are clearly needed to support detection of incipient AD in subjects with mild cognitive impairment (MCI). To date the most promising core candidate markers are total and hyperphosphorylated tau protein and amyloid beta peptides in the CSF, as well as hippocampus and whole brain volumetry using MRI. None of the candidates has been finally validated and established for clinical routine so far. International controlled multicenter cooperative studies are ongoing to further develop these core diagnostic marker candidates (phase III). The core markers are reviewed in detail. Promising novel approaches are discussed.
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PMID:[Neurobiological early diagnosis of Alzheimer's disease]. 1761 28

Acutely progressing dementia, generalized myoclonus, and periodic synchronous discharge (PSD) on EEG are thought to be characteristic features of Creutzfeldt-Jakob disease (CJD). However, recent surveillance studies in European countries and Japan have revealed several uncommon variants that run relatively long clinical course, demonstrate atypical myoclonus, and show no PSD. Brain specific proteins such as 14-3-3 protein, tau protein, and neuron specific enolase (NSE) are detected in the CSF of CJD patients. Clinical features and laboratory findings of sporadic CJD are related well to the combination of polymorphism at codon 129 of prion protein gene(PRNP) (Methionine/Methionine, Methionine/Valine, and Valine/Valine) and type of pathogenic prion protein (type 1 and type 2). Those of genetic prion disease depend on pathogenic mutation in PRNP. Positive rates of PSD and 14-3-3 protein in the CSF differ among subtypes of sporadic CJD and genetic prion diseases. Diffusion-weighted MRI is very useful for an early clinical diagnosis of CJD and some subtypes show their own characteristic findings.
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PMID:[Clinical characteristics and laboratory findings in prion diseases]. 1769 77

Prevention of Alzheimer disease (AD) is a national and global imperative. Therapy is optimally initiated when individuals are asymptomatic or exhibit mild cognitive impairment (MCI). Development of therapeutically beneficial compounds requires the creation of clinical trial methodologies for primary and secondary prevention. Populations in primary prevention trials selected only on the basis of age will have low rates of emergent MCI or AD. Epidemiologically based risk factors or biomarkers can be used to enrich trials and increase the likelihood of disease occurrence during the trial. Enrichment strategies for clinical trials with MCI include use of biomarkers such as amyloid imaging, MRI with demonstration of medial temporal lobe atrophy, bilateral parietal hypometabolism on PET, and reduced amyloid beta peptide and increased tau protein in CSF. Neuropsychological measures appropriate for trials of MCI may not be identical to those measures most suited for AD trials. Attention to these and other features of trial design, clinical assessment, and use of biomarkers is critical to improving the detection of disease-modifying effects of emerging therapies in presymptomatic or minimally symptomatic populations. The neurologic health of the growing aging population demands disease-modifying therapies and the development of methods to identify and test promising candidate agents.
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PMID:Disease-modifying therapies for Alzheimer disease: challenges to early intervention. 1793 73

In recent studies, patients diagnosed with Alzheimer's disease (AD) showed significantly elevated CSF levels of tau protein. Tau protein was therefore regarded as a putative molecular marker for AD. Since early diagnosis of AD is warranted for appropriate therapeutic intervention, investigation of total tau protein levels in patients with Aging Associated Cognitive Decline (AACD) and AD are reasonable. In our study the CSF concentrations of total tau protein were measured by ELISA in 132 patients with AD, 29 patients with AACD and 24 healthy controls. CSF concentrations were compared between the subgroups of mild, moderate and severe AD, AACD and the control group and were correlated with age and severeness of the illness. The concentration of total tau protein was increased significantly in patients with severe and moderate AD compared to all other groups. Within the group of AD patients, total tau protein correlated significantly with the severity of the dementia but not with age. Although the range of the measured tau protein concentrations is wide and overlapping between the diagnostic groups our data indicate that from a clinical point of view significantly increased tau protein levels confirm the clinical diagnosis of AD while normal values do not exclude it.
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PMID:[CSF levels of total tau protein in patients with mild cognitive impairment and Alzheimer's disease]. 1832 93

The neurodegenerative disorder Alzheimer's disease (AD) is the most common cause of dementia in the elderly. The presence of neurofibrillary tangles, consisting of hyperphosphorylated tau protein, is one of the major neuropathologic characteristics of the disease, making this protein an attractive biomarker for AD and a possible target for therapy. Here, we describe an optimized immunoprecipitation mass spectrometry method that enables, for the first time, detailed characterization of tau in human cerebrospinal fluid. The identities of putative tau fragments were confirmed using nanoflow liquid chromatography and tandem mass spectrometry. Nineteen tryptic fragments of tau were detected, of which 16 are found in all tau isoforms while 3 represented unique tau isoforms. These results pave the way for clinical CSF studies on the tauopathies.
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PMID:Characterization of tau in cerebrospinal fluid using mass spectrometry. 1835 40

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common causes of dementia in old people. They remain difficult to differentiate in practice because of lack of sensitivity and specificity of current clinical diagnostic criteria. Recent molecular and cellular advancements indicate that the use of cerebrospinal fluid markers may improve early detection and differential diagnosis of AD. Our objective in this study was to determine diagnostic accuracy of three cerebrospinal (CSF) markers: total tau protein (t-tau), tau protein phosphorylated on threonine 181 (p-tau181) and tau protein phosphorylated on serine 199 (p-tau199). Using commercially available ELISA kits concentrations of t-tau, p-tau181 and p-tau199 were analyzed in 12 patients with probable AD, 9 patients with VaD and 12 NC subjects. The median levels of all three markers were significantly higher in AD group versus VaD and NC groups. However, when the sensitivity levels were set to 85% or higher, only t-tau and p-tau199 satisfied consensus recommendations (specificity more than 75%) when differentiating AD from VaD. In conclusion, our preliminary data on a small group of selected subjects suggest that the CSF t-tau and p-tau199 levels are useful markers for differentiating AD from VaD.
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PMID:Cerebrospinal fluid markers in differential diagnosis of Alzheimer's disease and vascular dementia. 1840 55

We carried out a quantitative analysis of transthyretin (TTR), total tau protein and amyloid-beta (Abeta) peptide (1-40 and 1-42) in the lumbar cerebrospinal fluid of 106 patients with different forms of dementia including Alzheimer's disease (AD), Creutzfeldt-Jakob-disease (CJD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD) and normal pressure hydrocephalus (NPH) in comparison to healthy controls. Our study revealed that Abeta_{1-42} levels were decreased in all patients irrespective of dementia type. Tau protein levels were abnormal in all degenerative dementia except of NPH. Tau levels did not allow differential diagnosis of dementia type except for CJD, where we observed extremely high CSF levels. In other dementia types, levels were elevated in a similar range. Transthyretin levels were selectively decreased in AD and NPH, thus revealing the potential of this protein to be used as additional biomarker in the neurochemical differential diagnosis of AD. A significant negative correlation of TTR CSF levels and disease severity in AD was observed.
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PMID:Quantitative analysis of transthyretin, tau and amyloid-beta in patients with dementia. 1852 24

The chemokine CXCL12 (also known as stromal cell-derived factor 1, SDF-1) controls many aspects of bone marrow-derived stem cell functions and has been associated with neurogenesis as well with recruitment of brain resident and non-resident circulating cells towards sites of lesion in the central nervous system (CNS). Disrupting this line of chemokine-mediated intercellular communication may contribute to the pathogenesis of Alzheimer's disease (AD). In this study, decreased CXCL12 plasma levels in patients with early AD (p = 0.003) were found, which significantly inversely correlated with CSF tau protein levels (r = -0.373; p = 0.042) and positively with CXCL12 CSF levels (r = 0.429; p = 0.018) and with changes of cognitive functions over the time period of 15 months (r = 0.583; p = 0.009). Our findings indicate a lack of chemotactic activity in early AD and support the view of a deficient regenerative hematopoietic brain support in early AD with putative pathogenic and therapeutic relevance.
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PMID:Decreased CXCL12 (SDF-1) plasma levels in early Alzheimer's disease: a contribution to a deficient hematopoietic brain support? 1878 Sep 69

We report a patient with early-onset autosomal dominant dementia. The CSF showed increased levels of tau protein and decreased amyloid beta (ratio 42:40) typical for Alzheimer's disease. Cerebral MRI revealed vascular lesions and white-matter changes around the posterior horns of the ventricles with only moderate atrophy of the brain. Susceptibility-weighted imaging detected multiple small hemorrhagic changes. Gene analysis revealed amyloid precursor protein (APP) locus duplication as the cause of hereditary Alzheimer's dementia. The co-occurrence of CSF changes typical for Alzheimer's disease and MRI findings of cerebral amyloid angiopathy is remarkable, as it is also described for APP locus duplication. In conjunction with a family history suggestive of hereditary dementia, such a constellation should lead to enhanced gene analysis.
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PMID:[Hereditary Alzheimer's disease with amyloid angiopathy caused by amyloid precursor protein locus]. 1878 Dec 90

To assess the role of tau protein, beta-amyloid(1-42) and cystatin C in the diagnostics of Alzheimer dementia (AD) and other neurodegenerative diseases (ND) by comparing to the control groups (CG). The levels of tau protein, beta-amyloid(1-42) and cystatin C were assessed in the set of 69 patients (AD + ND, 33 males, 36 females, aged 22-90, mean 60.5 + 16.1 years), and in a control group of 69 subjects without the affection of the central nervous system (CGAD + CGND, 33 males, 36 females, aged 20-91, mean 60.5 + 16.0 years). Statistically significant increased tau protein levels (P = 0.0001) and index tau/beta-amyloid(1-42) levels (P = 0.0002) were shown in the group of AD patients, compared to the group of ND patients. One-way ANOVA analysis with Bonferonni post hoc test did not show any significant differences of the cystatin C values between any of the compared groups. ROC analysis showed at least one tie between the positive actual state group (AD) and the negative actual state group (ND) by CSF cystatin C and at least one tie between the positive actual state group and the negative actual state group by CSF tau protein. Our study confirmed previously reported results only in part. While tau protein seems to be quite a reliable marker of AD, the role of beta-amyloid(1-42) and cystatin C in AD diagnosis remains at least questionable.
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PMID:The assessment of beta amyloid, tau protein and cystatin C in the cerebrospinal fluid: laboratory markers of neurodegenerative diseases. 1915 49


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