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)

Argyrophilic grain disease (AGD) is a neurodegenerative disorder of the aged human brain associated with the formation of abnormal tau protein in specific neurones and macroglial cells. Previously, we reported the association between AGD and the epsilon2 allele of apolipoprotein E (ApoE). Here, the polymorphisms of the alpha-2 macroglobulin gene (A2M) and those of the low-density lipoprotein receptor-related protein gene (LRP) were assessed in 115 AGD cases and compared with 170 controls. The results reveal an association between AGD and the C766T polymorphism of LRP (P=0.001). In addition, the present study shows that the valine to isoleucine (Val1000Ile) polymorphism of A2M is linked with AGD (P=0.03). By comparison, no relationship between AGD and the intronic 5-bp deletion/insertion polymorphism of A2M is demonstrable (P=0.8). Finally, this report corroborates and extends our earlier finding in that the frequency of the epsilon2 allele of ApoE is higher in AGD cases than in controls (17.4% vs. 8.5%, P=0.003), whereas the epsilon4 allele frequency approximates that in control cases (13.9% vs. 13.2%, P=0.93). This association, however, is only apparent in the presence of the LRP CC genotype. In conclusion, the present study shows that AGD is associated with the LRP, A2M and ApoE genes.
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PMID:Genetic association of argyrophilic grain disease with polymorphisms in alpha-2 macroglobulin and low-density lipoprotein receptor-related protein genes. 1217 43

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

Cerebrospinal fluid (CSF) contains proteins known to be involved in the pathogenesis of Alzheimer disease (AD), including amyloid-related proteins, tau protein and apolipoprotein E. While the CSF concentrations of these proteins have been compared in subjects with and without dementia of the Alzheimer type (DAT), they have not been simultaneously assessed in carefully staged DAT subjects and control subjects to examine correlations among them. In this study, CSF concentrations of soluble amyloid precursor protein (sAPP), two forms of beta-amyloid protein (Abeta and Abeta ), tau, and apolipoprotein E were assessed in subjects with (n = 33) and without (n = 11) DAT. Direct correlations were found between CSF concentrations of sAPP and tau and Abeta, and between apolipoprotein E and Abeta within the DAT subjects and within the combined group of DAT and control subjects. A weak inverse correlation was also found between CSF concentrations of tau and Abeta within the combined group of DAT and control subjects. Moreover, increased severity of dementia was correlated with increased CSF tau concentrations and decreased sAPP and Abeta concentrations. Increased CSF concentrations of tau significantly discriminated DAT and control subjects, as did the ratios of tau to Abeta and tau to Abeta(1-42).
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PMID:Relationships among cerebrospinal fluid biomarkers in dementia of the Alzheimer type. 1221 44

The M1 muscarinic agonists AF102B, AF150(S) & AF267B--i) restored cognitive impairments in several animal models for AD with an excellent safety margin; ii) elevated alpha-APPs levels; iii) attenuated vicious cycles induced by A beta, and inhibited A beta- and oxidative stress-induced apoptosis; and iv) decreased tau hyperphosphorylation. AF150(S) and AF267B were more effectve than rivastigmine and nicotine in restoring memory impairments in mice with small hippocampi. In apolipoprotein E-knockout mice, AF150(S) restored cognitive impairments and cholinergic hypofunction and decreased tau hyperphosphorylation. In aged microcebes, AF150(S) restored cognitive and behavioral impairments and decreased tau hyperphosphorylation, paired helical filaments and astrogliosis. In rabbits, AF267B & AF150(S) decreased CSF A beta(1-42 & 1-40), while AF102B reduced A beta(1-40). Finally AF102B decreased CSF A beta(total) in AD patients. Taken together, M1 agonists may represent a unique therapy in AD due to their beneficial effects on three major hallmarks of AD--cholinergic hypofunction, A beta and tau protein hyperphosphorylation.
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PMID:Impact of muscarinic agonists for successful therapy of Alzheimer's disease. 1245 63

The total amount of hyperphosphorylated tau protein (p-tau load), present as neurofibrillary tangles (NFTs), neuropil threads or plaque neurites, was quantified in the frontal cortex of 109 cases of sporadic Alzheimer's disease (AD) and 35 cases of familial AD due to missense mutations in the presenilin-1, presenilin-2 and amyloid precursor protein genes. p-tau load was inversely correlated with age at onset of illness in both sporadic and familial AD but not with duration of disease. There was no difference in p-tau load between cases of familial AD and others with sporadic AD, matching the familial cases for apolipoprotein E (APO E) genotype. However, p-tau was greater in cases of familial and sporadic AD in the presence of APO E epsilon4 allele and increased with gene dose. Conversely, p-tau load tended to be lower when epsilon2 allele was present. In sporadic AD, tau load was highly significantly correlated with amyloid beta40 (Abeta40), but not Abeta42(43), load. These data indicate that the burden of pathological tau deposited in the brain in both familial and sporadic AD is favoured in the presence of APO E epsilon4 allele and also related to the amount of Abeta40, this also being higher when epsilon4 allele is present. Abeta40 plaques are rich in microglial cells and it is possible that p-tau pathology in AD is triggered by reaction of microglial cells to the presence of Abeta40 and not this peptide directly.
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PMID:Tau load is associated with apolipoprotein E genotype and the amount of amyloid beta protein, Abeta40, in sporadic and familial Alzheimer's disease. 1258 38

The apolipoprotein E (apoE) epsilon 4 allele is associated with an increased risk of sporadic as well as late-onset familial Alzheimer's disease (AD). To accurately determine the isoform-specific effects of human apoE on AD-like phosphorylation of tau, hippocampi from human apoE knock-in (KI) mice were studied by quantitative immunoblotting. There was no significant difference in phosphorylation levels of tau at nine of the 13 epitopes, for six of eight tau kinases, or in protein levels of three tau phosphatases, between apoE3-KI and apoE4-KI mouse hippocampi. However, in apoE4-KI mice, phosphorylation of tau at Ser235 was increased to approximately 150%, that at Ser413 to approximately 140%, while that at Ser202/Thr205 and Thr205 were decreased to approximately 70%, and the protein level of tau protein kinase I/glycogen synthase kinase 3beta (TPKI/GSK3beta) was increased to approximately 120%, that of extracellular signal-regulated kinase 2 (ERK2) was increased to approximately 130%, compared with apoE3-KI mice.
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PMID:Phosphorylation state of tau in the hippocampus of apolipoprotein E4 and E3 knock-in mice. 1269 66

Subjects with mild cognitive impairment (MCI) are at a high risk of developing clinical Alzheimer's disease (AD). We asked to what extent the core biomarker candidates cerebro-spinal fluid (CSF) beta-amyloid(1-42) (Abeta(1-42)) and CSF tau protein concentrations predict conversion from MCI to AD. We studied 52 patients with MCI, 93 AD patients, and 10 healthy controls (HC). The MCI group was composed of 29 patients who had converted to AD during follow-up, and of 23 patients who showed no cognitive decline. CSF Abeta(1-42) and tau protein levels were assessed at baseline in all subjects, using enzyme-linked immunosorbent assays. For assessment of sensitivity and specificity, we used independently established reference values for CSF Abeta(1-42) and CSF tau. The levels of CSF tau were increased, whereas levels of Abeta(1-42) were decreased in MCI subjects. Abeta(1-42) predicted AD in converted MCI with a sensitivity of 59% and a specificity of 100% compared to HC. Tau yielded a greater sensitivity of 83% and a specificity of 90%. In a multiple Cox regression analysis within the MCI group, low baseline levels of Abeta(1-42), but not other predictor variables (tau protein, gender, age, apolipoprotein E epsilon4 carrier status, Mini Mental Status Examination score, observation time, antidementia therapy), correlated with conversion status (P<0.05). Our findings support the notion that CSF tau and Abeta(1-42) may be useful biomarkers in the early identification of AD in MCI subjects.
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PMID:Value of CSF beta-amyloid1-42 and tau as predictors of Alzheimer's disease in patients with mild cognitive impairment. 1469 32

With the development of new therapeutic strategies, and the concept of mild cognitive impairment (MCI) as an early stage of Alzheimer's disease (AD), there is an increasing need for an early and accurate diagnosis of sporadic AD. Therefore, biological markers allowing a positive diagnosis early in the course of the disease are highly desirable. The most extensively evaluated markers of sporadic AD are amyloid-beta proteins and levels of both total and phosphorylated microtubule-associated protein tau. In this study, we review the currently available data on the aforementioned markers assessed in the cerebrospinal fluid or plasma, alone and in combinations, focusing on their clinical applicability including sensitivity in the diagnosis of AD and mild cognitive impairment, specificity in discriminating AD from other dementias and correlations with the disease progression and apolipoprotein E genotype. We also analyze advantages and potential drawbacks of using biomarkers in the laboratory diagnosis of AD.
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PMID:Amyloid-beta and tau proteins as biochemical markers of Alzheimer's disease. 1519 Jun 80

Calcium deficiency due to insufficient nutritional intake, poor intestinal absorption or excessive urinary loss leading to secondary hyperparathyroidism, increase of calcium influx into nerve cells causing cell death may lead to neuronal dysfunction and cell death as in dialysis encephalopathy with EEG changes and decrease of nerve conduction velocity in chronic renal failure and Alzheimer's disease in aging. Intracellular free calcium (Ca i) is increased in nerve cells showing neurofibrillar tangles associated with tau protein in Alzheimer's disease. Increase of Ca i facilitates presenilin mutation with consequent augmentation of short chain amyloid beta production which further increase Ca i. Peroxide radical production by amyloid beta and metals such as Fe, Cu and Mn is prompted by an increase of Ca i. Plasma membrane damage caused by lipid peroxidation further increases Ca i. Neurotoxic action of apolipoprotein E(4) increasing the risk for Alzheimer's disease may be explained by lipid peroxidation and rise of Ca i. Beneficial effect of estrogen in preventing Alzheimer's disease may also be explained by its anti-oxidant effect and stimulation of intestinal calcium absorption. By increasing calcium intake and administration of active form of vitamin D which cannot be sufficiently supplied by the aging kidney, one step forward should be made in the prevention and treatment of Alzheimer's disease.
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PMID:[Alzheimer disease and calcium]. 1557 64

More than 180 genes distributed across the human genome are potentially involved in the pathogenesis of Alzheimer's disease (AD). The AD population shows a higher genetic variation rate than the control population. Significant differences in allelic distribution and frequency exist when AD-related polygenic clusters are compared with other forms of dementia, indicating that the genetic component in neurodegenerative dementia differs from that of other CNS disorders. The characterization of AD genotype-related phenotypic profiles reveals substantial differences in biological markers among AD clusters associated with different genes and/or allelic combinations. AD and dementia with vascular component (DVC) are the most prevalent forms of dementia. Both clinical entities share many similarities, but they differ in their major phenotypic and genotypic profiles, as revealed by structural and functional genomics studies. Comparative phenotypic studies have identified significant differences in 25% of more than 100 parametric variables, including anthropometric values, cardiovascular function, blood pressure, lipid metabolism, uric acid metabolism, peripheral calcium homeostasis, liver function, alkaline phosphatase, lactate dehydrogenase, red and white blood cells, regional brain atrophy, and brain blood flow velocity. Functional genomic studies incorporating apolipoprotein E (APOE)-related changes in biological markers extended the difference between AD and DVC by up to 57%. Structural genomic studies with AD-related genes, including APP, MAPT, APOE, PS1, PS2, A2M, ACE, AGT, cFOS, and PRNP, demonstrate different genetic profiles in AD and DVC, with an absolute genetic variation rate in the range of 30-80%, depending upon genes and genetic clusters. The relative polymorphic variation in genetic clusters integrated by two, three or four genes associated with AD ranges from 1 to 3%. The main phenotypic differences in AD are genotype dependent, indicating a powerful influence of polygenic factors on the AD phenotypic profile. All these genotypic and phenotypic variations bring about important consequences for the pharmacogenomics of AD.
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PMID:Genomic characterization of Alzheimer's disease and genotype-related phenotypic analysis of biological markers in dementia. 1558 76


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