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)

Potential cerebrospinal fluid (CSF) markers for Alzheimer's disease (AD) include tau protein, the 42 amino-acid form of amyloid beta (amyloid beta(1-42)) and apolipoprotein E (apoE). To study new aspects of these protein markers, we examined consecutive CSF samples from 26 patients with acute ischemic stroke. CSF samples were taken on day 0-1, day 2-3, day 7-9, 3 weeks and 3-5 months after the stroke. CSF-tau showed a marked increase day 2-3, which peaked after 1 week and returned to normal after 3-5 months. CSF-tau also showed correlation (r=0.95; p<0.01) with the size of the infarct. In contrast, CSF-amyloid beta(1-42) and CSF-apoE showed no significant changes during the period. The marked increase in CSF-tau levels after acute ischemic stroke indicate that CSF-tau reflect the degree of neuronal damage. The reason for unchanged levels of CSF-amyloid beta(1-42) and CSF-apoE after ischemic stroke remains unclear.
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PMID:Cerebrospinal fluid markers for Alzheimer's disease evaluated after acute ischemic stroke. 1221 84

The numerous advances in the understanding of the neurobiology of Alzheimer's disease in the past 15 years have suggested many new potential targets for therapeutic intervention. This article gives a broad overview of the spectrum of targets for AD treatment, with particular emphasis on amyloid beta-peptides and tau protein.
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PMID:Alzheimer's disease: targets for drug development. 1236 53

The neuropathological features associated with Alzheimer's disease (AD) brain include the presence of extracellular neuritic plaques composed of amyloid beta protein (Abeta), intracellular neurofibrillary tangles containing phosphorylated tau protein and the loss of basal forebrain cholinergic neurons which innervate regions such as the hippocampus and the cortex. Studies of the pathological changes that characterize AD and several other lines of evidence indicate that Abeta accumulation in vivo may initiate phosphorylation of tau protein, which by disrupting neuronal network may trigger the process of neurodegeneration observed in AD brains. However, the underlying cause of degeneration of the basal forebrain cholinergic neurons and their association, if any, to Abeta peptides or phosphorylated tau remains mostly unknown. In the present study, using rat primary septal cultures, we have shown that aggregated Abeta peptides, in a time (18-96 h)- and concentration (0.7-60 microM)-dependent manner, induce toxicity and decrease choline acetyltransferase enzyme activity in cultured neurons. Using immunocytochemistry and immunoblotting, we have also demonstrated that Abeta treatment can significantly increase the phosphorylation of tau protein in septal cultures. At the cellular level, hyperphosphorylated tau is mostly apparent in the somatodendritic compartment of the neurons. Abeta peptide (10 microM), in addition to tau phosphorylation, also activates mitogen-activated protein kinase and glycogen synthase kinase-3beta, the two kinases which are known to be involved in the formation of hyperphosphorylated tau in the AD brain. Exposure to specific inhibitors of the mitogen-activated protein kinase (i.e. PD98059) or glycogen synthase kinase-3beta (i.e. LiCl) attenuated the hyperphosphorylation of the tau protein in cultured neurons. Given the evidence that tau phosphorylation can induce cell loss by disrupting neuronal cytoskeleton, it is likely that aggregated Abeta peptide triggers degeneration of septal neurons, including those expressing the cholinergic phenotype, by phosphorylation of the tau protein activated by mitogen-activated protein kinase and glycogen synthase kinase-3beta. These results, taken together, suggest that cultured septal cholinergic neurons are vulnerable to Abeta-mediated toxicity and tau phosphorylation may play an important role in Abeta-induced neurodegeneration.
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PMID:Amyloid beta peptide induces tau phosphorylation and loss of cholinergic neurons in rat primary septal cultures. 1240 34

Biological markers are important tools in identifying predisposing factors to disease, as diagnostic tests, and in monitoring disease progression. Alzheimer disease is believed to have a long preclinical phase, followed by mild cognitive impairment, and, finally, dementia. Detecting alterable predisposing factors or identifying patients in preclinical or early-stage illness offers the greatest potential to modifying disease course. The authors focus on: 1) predisposing factors, such as genetic risk factors and homocysteine; 2) laboratory markers, such as amyloid beta and tau protein; and 3) diagnostic markers, such as structural and functional neuroimaging. Many markers have been tested but have not been confirmed in subsequent studies. Other tests require complex and expensive laboratory evaluation or expertise, thereby limiting their use at present. Still others are markers only useful in later-stage illness. Nonetheless, the search for markers has increased our understanding of the biology of illness and has led to exciting new directions, with diagnostic as well as treatment implications.
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PMID:Biological markers in Alzheimer disease. 1242 75

Alzheimer disease(AD) is characterized as neurodegenerative disease showing impairment of cognitive function, death of neuronal cells, numerous numbers of senile plaques and tangle of neurofilaments. There are two different hypotheses that neurotoxicity of aggregated amyloid beta protein(A beta) and hyperphosphorylation of tau protein are the causes of AD. The dysfunction of cholinergic neuronal system is observed in the early stage of AD. Therefore, the strategy to increase of acetylcholine (ACh) level in brain by using ACh esterase inhibitor is mainstream in the present. We have tacrine, donepezil, rivastigmine and galantamine. Tacrine, the first drug for AD, is replaced by other drugs, because of its hepatic toxicity. Galantamine binds allosteric sites of nicotine receptor and stimulates it in addition to its inhibitory effect on ACh esterase. Metamantine was approved in EU in 2002. It is non-competitive inhibitor of NMDA receptors, and dopamine releaser, which has neuroprotective effect. All of the above drugs improve cognitive function of patients, and they could delay hospitalization for 7 months or more. In the present anti-inflammatory drugs, anti-oxidative drugs and estrogen are under investigation. As anti-A beta therapy, inhibitors of beta -and gamma-secretase, A beta aggregation inhibitors, A beta degradation stimulators and A beta vaccination are possible strategies. The inhibitors of tau protein phosphorylation and activators of phosphates could be that of anti-tau protein phosphorylation. Additionally, it is expected to have the strategies such as neuroregeneration by neurotorophic factors and immunopyline ligands, and supply of neuronal cells by gene therapy and human ES cells.
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PMID:[Anti-dementia drugs for Alzheimer disease in present and future]. 1249 71

Cerebrospinal fluid (CSF) levels of tau protein and amyloid beta(1-42) peptide (Abeta42) have been suggested as possible diagnostic markers of Alzheimer's disease (AD). In order to evaluate their diagnostic potential in clinical practice, we measured tau and Abeta42 levels in the CSF of 49 AD patients, 15 patients with non-AD neurodegenerative dementias (NAND), six patients with vascular dementia (VD) and 49 elderly controls. All the subjects were of Greek origin. A marked increase in tau, a decrease in Abeta42 and a marked increase in the tau/Abeta42 ratio was noted in AD. Abeta42 alone had a specificity of 80% and a sensitivity of 82% in differentiating AD from normal ageing, whilst the corresponding values for differentiating AD from NAND or VD were 80 and 71, or 67 and 82%, respectively. Tau was better in differentiating AD, from normal ageing (specificity 96%, sensitivity 88%), NAND (specificity 93%, sensitivity 71%) and VD (specificity 83%, sensitivity 94%). The tau/Abeta42 ratio achieved values comparable or even better than tau for differentiating AD from normal ageing (specificity 86%, sensitivity 96%) and VD (specificity 83%, sensitivity 90%) and definitely better than any of the candidate markers alone, for differentiating AD from NAND (specificity 100%, sensitivity 71%). Thus, the combined use of CSF tau and Abeta42 in the form of the tau/Abeta42 ratio is a simple, safe and useful adjuvant to clinical criteria for dementia diagnosis.
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PMID:CSF tau protein and beta-amyloid (1-42) in Alzheimer's disease diagnosis: discrimination from normal ageing and other dementias in the Greek population. 1260 86

The diagnostic significance of tau proteins in cerebrospinal fluids (CSF) has been described in many cases of dementia of Alzheimer type (AD). However, in patients with other diseases showing neurofibrillary tangles (NFT) similar to those in AD, tau proteins in cerebrospinal fluids have not been rigorously investigated. In particular, differentiating corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) is clinically and pathologically difficult, and a useful biochemical marker to discriminate these two diseases has been a subjects of clinical interest. Therefore, we examined the usefulness of CSF tau and amyloid beta (A beta) proteins for the differentiation between CBD and PSP. CSF total tau (t-tau) and A beta proteins were measured with the sandwich ELISA method (Innogenetics, Belgium). CSF tau protein phosphorylated at serine 199 (p-tau) was measured by a recent established sandwich ELISA (Mitsubishi Chemical Co.). In conclusion, measurement of tau protein levels in CSF may be useful for the differential diagnosis of CBD from PSP. We also suggest that CSF p-tau may be a better biochemical marker than CSF t-tau.
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PMID:[Corticobasal degeneration and progressive supranuclear palsy--biochemical marker]. 1278 94

Quantitative neuropsychiatry has provided increasingly precise descriptions of behavioral phenotypes associated with neurodegenerative disorders. Degenerative diseases of the brain are disturbances of protein metabolism, with failure of protein degredation by the ubiquitin-proteosome system, production of neurotoxic peptide oligomers, and accumulation of intracellular protein deposits. Abnormalities of amyloid beta peptide, alpha-synuclein protein, and hyperphosphorylated tau protein account for more than 90% of degenerative dementias. Functionally related neuroanatomical systems have shared metabolic characteristics and common vulnerabilities to protein dysmetabolism, providing the basis for phenotypes that reflect the underlying proteotype. Patients with alpha-synuclein disorders are particularly prone to hallucinations, delusions, and rapid eye movement sleep behavior disorder. Patients with tauopathies manifest disproportionate disinhibition and apathy, and may exhibit compulsions. Alzheimer's disease is a triple proteinopathy with abnormalities of A-beta, tau, and alpha-synculein leading to a complex behavioral phenotype. This molecular approach to neuropsychiatry may assist in understanding the mechanisms of degenerative diseases, provide insight into the pathophysiology of neuropsychiatric symptoms, and contribute to monitoring disease-modifying therapies.
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PMID:Toward a molecular neuropsychiatry of neurodegenerative diseases. 1289 66

Alzheimer's disease (AD) is characterized by memory impairment leading to dementia, deposition of amyloid plaques and neurofibrillary tangles (NFTs), and neuronal loss. The major component of plaques is the amyloid beta peptide, A beta, whereas NFTs contain hyperphosphorylated forms of the microtubule-associated protein tau (tau). Familial AD (FAD) mutations either elevate A beta synthesis by favoring 'secretase' of the Alzheimer beta-amyloid precursor protein (APP) or enhance the fibrillogenic properties of this peptide. Mutations in the tau gene cause a different disease denoted FTPD-17, but suggest that the aberrant forms of tau seen in AD are unlikely to be benign. These findings imply a complex pathogenic cascade in AD and important goals of transgenic modeling are to capture and stratify this pathogenic process. Several laboratories have created APP transgenic (Tg) mice that exhibit AD-like amyloid pathology and A beta burdens. These Tg lines also exhibit deficits in spatial reference and/or working memory, with immunization against A beta attenuating both AD-associated phenotypes. Tangle-like pathologies are observed in mice expressing FTPD-17 mutant forms of tau, but florid tau pathologies based upon the wild type (wt) tau isoforms present in AD have proven more elusive. Creation of animal models with robust amyloid and tau pathologies, yet free of irrelevant confounding pathologies, remains a major objective in this field.
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PMID:Mouse models of Alzheimer's disease: the long and filamentous road. 1450 12

We experimentally modeled neuronal cholesterol imbalance by creating an acute biochemical increase in cholesterol turnover in rat hippocampal slices. This kind of experimental set-up impairs the redistribution of cholesterol from one cell to another via lipoprotein transport. While increasing cholesterol removal or immediately afterwards, we evoked and recorded two brain waveforms, paired pulse facilitation (PPF) and long-term potentiation (LTP), which indicate neurotransmission and synaptic plasticity, respectively. We found that the lack of cholesterol supply to neurons impaired both PPF and LTP. From additional immunofluorescent analysis of the slices, we could demonstrate that the cholesterol imbalance also caused neurodegeneration of hippocampal neural cell processes and the appearance of tau protein pathology in the mossy fibers. We also analyzed rats fed a cholesterol diet and discovered that they had increased hippocampal cholesterol biosynthesis and impaired LTP. Cholesterol-fed rats were also characterized by Alzheimer's-like brain amyloid that we did not observe in the model of acute cholesterol imbalance. Our data and research by others suggest that biological cholesterol homeostasis dysregulation itself plays a key role in synaptic plasticity impairment and neuronal degeneration, and is the primary cause for several Alzheimer's disease hallmarks not limited to brain amyloids. Moreover, changes in the neurochemistry of amyloid beta, tau, neuronal cytoskeleton, and oxidative stress reactions due to Alzheimer's likely represent physiological transitory mechanisms that aim to compensate impaired brain cholesterol dynamics and/or associated neurotransmission and synaptic plasticity failure. Part of this article was published as netprint and is available under the URL http://clinmed.netprints.org/cgi/content/full/2001100005v1.
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PMID:Cholesterol, synaptic function and Alzheimer's disease. 1457 23


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