Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixteen brains from Alzheimer's disease (AD) patients with varying duration of dementia were studied using the monoclonal antibody (mAb) 6.423 raised against the three repeated domains of the tau protein, and named the paired helical filament (PHF) core. In Ammon's horns of the AD cases 6.423 mAb, in addition to immunoreacting with neurofibrillary tangles (NFTs), dystrophic neurites, and plaquelike structures, also recognized a subpopulation of granulovacuolar degeneration elements (GVD). A new immunoreactive structure, a spherical inclusion, was also stained by 6.423. The immunoreactive GVD elements and the spherical inclusion were found in the aged controls (greater than 65 years of age) and in non-AD dementia cases, as well. The staining of the GVD was markedly decreased when the tissue was preincubated with alkaline phosphatase. In contrast, NFTs and the spherical inclusions resisted dephosphorylation. Neurons containing the spherical inclusion frequently lacked immunoreactive intracellular NFTs. Due to the similar immunohistochemical properties between the spherical bodies and immunoreactive NFTs, we named this new inclusion PHF core body. Our results suggest that the PHF core body may represent a successful attempt by hippocampal neurons to restrict the PHF core expression. Thus, the failure of this mechanism may lead to the NFT formation in a range of dementing processes. Alternatively, the PHF core body may be an early stage in the NFT formation.
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PMID:New patterns of intraneuronal accumulation of the microtubular binding domain of tau in granulovacuolar degeneration. 132 97

The most characteristic cellular change in Alzheimer's disease is the accumulation of aberrant filaments, the paired helical filaments (PHF), in the affected neurons. There is growing evidence from a number of laboratories that dementia correlates better with the accumulation of PHF than of the extracellular amyloid, the second major lesion of Alzheimer's disease. PHF are both morphologically and biochemically unlike any of the normal neurofibrils. The major polypeptides in isolated PHF are microtubule-associated protein tau. Tau in PHF is phosphorylated differently from tau in microtubules. This abnormal phosphorylation of tau in PHF occurs at several sites. The accumulation of abnormally phosphorylated tau in the affected neurons in Alzheimer's disease brain precedes both the formation and the ubiquitination of the neurofibrillary tangles. In Alzheimer's disease brain, tubulin is assembly competent, but the in vitro assembly of microtubules is not observed. In vitro, the phosphate groups in PHF are less accessible than those of tau to alkaline phosphatase. The in vitro dephosphorylated PHF polypeptides stimulate microtubule assembly from bovine tubulin. It is hypothesized that a defect in the protein phosphorylation/dephosphorylation system is one of the earliest events in the cytoskeletal pathology in Alzheimer's disease. Production of nonfunctional tau by its phosphorylation and its polymerization into PHF most probably contributes to a microtubule assembly defect, and consequently, to a compromise in both axoplasmic flow and neuronal function. Index Entries: Alzheimer's disease; mechanisms of neuronal degeneration; neurofibrillary changes; paired helical filaments: biochemistry; microtubule-associated protein tau; abnormal phosphorylation; ubiquitination; microtubule assembly; axoplasmic flow; protein phosphorylation/dephosphorylation.
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PMID:Ubiquitination and abnormal phosphorylation of paired helical filaments in Alzheimer's disease. 172 45

A 37-year-old female was admitted to our hospital because of progressive dementia and gait disturbance. She was healthy until 34 years of age when she had difficulty in walking and memory disturbance with personality changes. At age 36, she developed urinary incontinence and dementia. The neurological examination demonstrated euphoric mental state, emotional incontinence, severe dementia, paraplegia, dysmetria, choreic movements in both arms and urinary incontinence. Diffuse hyperreflexia and bilateral Babinski signs were observed. Routine laboratory examination showed slightly increased erythrocyte sedimentation rate and alkaline phosphatase. Electroencephalogram revealed diffuse irregular slow waves. X-ray film of the ulnar bone revealed osteoporotic and cystic lesions. The biopsy of the left tibial bone showed a specific membranous cystic structure. Computerized tomography (CT) of the brain showed symmetric, diffuse low density areas in the cerebral white matter and severe atrophy of the cerebellum. T2-weighted magnetic resonance imaging (MRI) revealed diffuse high intensity areas in the cerebral white matter. The present case is characterized by diffuse changes in cerebral white matter and cerebellar atrophy, which have been never reported in Nasu-Hakola disease. The diffuse cerebral white matter changes shown by CT and MRI appear to indicate that this patient is the first case of leukodystrophy of sudanophilic type since the original case reported by Nasu et al.
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PMID:[A case of membranous lipodystrophy (Nasu) with diffuse cerebral white matter involvement and cerebellar atrophy on brain CT and MRI]. 208 28

Changes in microvascular dimensions occurring with normal aging and Alzheimer's dementia were measured in thick sections of postmortem human visual cortex stained for alkaline phosphatase. Capillary density was decreased to the same degree in both normal aged and demented aged subjects. The fields selected for analysis in both groups included all cortical laminae and, where possible, amyloid-cored neuritic plaques. The mean density of such plaques in these selected fields was slightly but not significantly higher in the demented group. In both groups plaques were more plentiful in visual laminae with the highest capillary densities (II-IV), but plaques and vessels were closer to each other in the normal aged than in the demented. Plaque distributions differed; in the normal aged, plaques concentrated in lamina IV; in the demented they were more evenly spread throughout the laminae. Plaque cores were larger in the demented. Amyloid angiopathy was more common and more extensive in the demented group; amyloid-cored plaques were not closely associated with affected vessels. Plaque distributions in Alzheimer subjects with and without amyloid angiopathy differed; plaque density was greatest in those without angiopathy. Alzheimer's dementia was not associated with any decline in microvascularity. Plaque concentration in well vascularized laminae suggests a pathogenetic role for some blood-borne agent. Differences in plaque distributions imply that the role or the agent differs in normal and demented aging, or perhaps between cases with and without amyloid angiopathy.
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PMID:Neuritic plaques and vessels of visual cortex in aging and Alzheimer's dementia. 238 95

Cerebral cortical microvessels were prepared from control, dementia of Alzheimer type (AD/SDAT) and multi-infarct dementia (MID) autopsy cases. The microvessel yields were approx. 200 micrograms protein/g starting material, and did not differ significantly between control, MID and AD/SDAT groups. The purity of the preparations was confirmed both by light and electron microscopy and by measurement of enrichment of the endothelial markers gamma-glutamyltranspeptidase and alkaline phosphatase. Higher microvessel alkaline phosphatase activities and higher microvessel/homogenate ratios of activities of both enzymes in the MID and the AD/SDAT samples than in the control samples were found, which may be consistent with previous findings of structural abnormalities of the cerebral endothelial cells in AD/SDAT. The levels of [3H]prazosin binding did not differ significantly between control. MID and AD/SDAT samples at any [ligand] tested (0.05, 0.1, and 0.5 nM), suggesting conservation of microvessel alpha 1-adrenoceptors in MID and AD/SDAT.
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PMID:Alpha 1-adrenergic receptor binding sites in post-mortal human cerebral microvessel preparations: preservation in multi-infarct dementia and dementia of Alzheimer type. 255 46

Adherent human embryo brain cells have been infected with HIV. Cells replicating HIV were maintained in culture for seven sequential passes over 7 months and continued to produce HIV during that time. Human embryo brain cells displayed glial-cell morphology and expressed glial fibrillary acidic protein. Electron microscopy showed clusters of virus particles around these cells as well as budding virus. Extracted, infected glial cells revealed bands for three major gag proteins, p18, p24 and p55, in Western blotting. It was not possible to detect CD4 antigen on the surface of these cells by indirect immunofluorescence or alkaline phosphatase staining with CD4 monoclonal antibodies. The results of these experiments indicate that HIV replicates in non-malignant brain cells. This observation strengthens the postulated aetiological link between HIV and the encephalopathy, dementia and other neurological symptoms observed in HIV-infected patients.
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PMID:HIV replicates in cultured human brain cells. 312 70

The diameters and densities of capillaries and arterioles in the hippocampal cortex of normal subjects and patients with Alzheimer's dementia were measured in thick celloidin sections stained for alkaline phosphatase. Microvascular diameters in general are affected more by age than by the presence of dementia of the Alzheimer type. The diameter of both capillaries and arterioles increases significantly with age. The density of capillaries decreases whereas that of the arterioles increases significantly. The capillary changes suggest that a reduced exchange potential accompanies ageing. In brains of people with Alzheimer's disease the overall capillary diameters and densities do not differ from those of age-matched controls. Regional changes may, however, be important: those hippocampal zones showing the greatest severity of or increment in nerve cell lesions do correspond to those having the highest levels of or increase in capillary density and the greatest decrease in diameter, suggesting a direct association between neuronal susceptibility to Alzheimer changes and degree of regional blood supply. Capillary surface areas, volumes and area/capillary volume ratios support the possibility of this relationship. Neurofibrillary tangles and granulovacuolar degeneration do not correlate equally with the degree of capillary "irrigation"; tangles are more closely related to these morphological vascular parameters.
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PMID:Morphometric comparison of hippocampal microvasculature in ageing and demented people: diameters and densities. 722 73

The examination of five pediatric patients with encephalopathy secondary to chronic renal failure has indicated a stereotyped sequence of neurologic signs and symptoms including ataxia, loss of motor abilities, myoclonus, seizures, dementia, and bulbar dysfunction. Both the patients with CNS dysfunction and a control group selected for a similar degree of renal failure had increased levels of serum phosphate, alkaline phosphatase, and parathyroid hormone. Serial EEGs in the affected group revealed progressive slowing and an increase in paroxysmal features. No specific neuropathologic findings were noted in one patient.
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PMID:Encephalopathy in infants and children with chronic renal disease. 729 12

Significant osteoporosis determined by skeleton radiography and bone densitometry was found in 15 patients with cerebrotendinous xanthomatosis (CTX) whose mean age was 31 +/- 11 years. In three CTX patients, bone biopsies confirmed osteoporosis. Nine patients also sustained bone fractures following minimal trauma. Serum 25-hydroxyvitamin D ([25-OHD] 14.6 +/- 6.6 ng/mL v [normal] 30.4 +/- 8.0 ng/mL; P < .001) and 24,25-dihydroxyvitamin D ([24,25(OH)2D] 1.2 +/- 0.4 ng/mL v [normal] 2.7 +/- 0.8 ng/mL; P < .001) levels were low. Serum concentrations of 1,25(OH)2D, calcium, inorganic phosphorus, alkaline phosphatase, parathyroid hormone, and calcitonin were normal. Patients showed classic manifestations of CTX, including dementia, pyramidal and cerebellar insufficiency, peripheral neuropathy, cataracts, and tendon xanthomas associated with elevated serum cholestanol concentrations. These results demonstrate that extensive osteoporosis and increased risk of bone fractures are components of this inherited disease.
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PMID:Osteoporosis and increased bone fractures in cerebrotendinous xanthomatosis. 823 48

Different mutations in the microtubule-associated tau protein gene have recently been identified in several families with hereditary frontotemporal dementia and Parkinsonism (FTDP-17) linked to chromosome 17q21-22. Some families show neuronal and glial deposits containing hyperphosphorylated tau in several brain regions. We have investigated the presence of tau deposits by using a panel of anti-tau antibodies in three brains of a family with the P301L mutation (HFTD1) and in another family with the G272V mutation (HFTD2) of the tau gene. Numerous intracytoplasmic tau deposits in neurons, glial cells, and neurites were found in hippocampal formation, neocortex, and substantia nigra. These deposits in three patients from HFTD1 consisted of slender twisted filaments 15 nm wide with variable periodicity and a few straight filaments. Tau extracted from these filaments appeared as two major bands of 64 and 68 kd and a minor band of 72 kd that, after alkaline phosphatase treatment, proved to consist mainly of 4-repeat tau isoforms and one of the 3-repeat isoforms. In three patients from HFTD2 numerous Pick-like bodies were present. The conclusion is that the type and distribution of tau deposits in HFTD1 and HFTD2, the physical structure of filaments, and tau isoform composition in HFTD1 differ from Alzheimer's disease and an FTDP-17 family with a V337M mutation in the tau gene.
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PMID:Tau pathology in two Dutch families with mutations in the microtubule-binding region of tau. 981 25


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