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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 106 (1999), S. 513-523 
    ISSN: 1435-1463
    Keywords: Keywords: Alzheimer's disease ; cholinergic system ; degeneration ; phosphorylation ; tau.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. To assess a potential relationship between cortical neurofibrillary degeneration and cortical cholinergic deafferentation, the load of PHF-tau was analysed in eight cortical regions and in the basal nucleus of Meynert in 12 cases with Alzheimer's disease by means of a sensitive ELISA employing the monoclonal antibody B5-2. The activity of choline acetyltransferase was determined on identical tissue samples. The results demonstrate a highly correlative relationship between the cortical distribution of the amount of PHF-tau, mainly present in neuropil threads, and cholinergic depletion early during the course of the disease. This relationship was less strong in more advanced stages. The results support the suggestion that the formation of PHF-tau in cholinergic axon terminals which might result in a loss of cholinergic synapses and a cholinergic dysconnection of the cortex, is an early event in AD. During the progression of the disease, formation of PHF-tau appears to spread over the cortex which results in a more even distribution of neuropil threads and a progressive involvement of non-cholinergic neurons.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 106 (1999), S. 499-511 
    ISSN: 1435-1463
    Keywords: Keywords: Alzheimer's disease ; glycolysis ; 6-phosphofructokinase ; glial fibrillary acidic protein.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. The activities of hexokinase, aldolase, pyruvate kinase, lactate dehydrogenase and glucose 6-phosphate dehydrogenase were determined in brains of patients with Alzheimer's disease (AD) and in age matched controls. For pyruvate kinase and lactate dehydrogenase a significant increase in specific activity was found in frontal and temporal cortex of AD brains, while the activities of aldolase and hexokinase are not changed. Glucose 6-phosphate dehydrogenase activity was significantly reduced in hippocampus. The increase of some glycolytic enzyme activities is correlated with increased contents of lactate dehydrogenase and glial fibrillary acidic protein (GFAP) in homogenates of frontal and temporal cortex and elevated phosphofructokinase (PFK) and GFAP in astrocytes from the same brain areas. The data extend previous findings on an increase in brain PFK specific activity in AD and suggest that the increased activity of some glycolytic enzymes may be, at least in part, the result of the reactive astrocytosis developing in the course of AD.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 107 (2000), S. 451-461 
    ISSN: 1435-1463
    Keywords: Keywords: Primary guinea pig neurons, okadaic acid, metabolic labelling, amyloid precursor protein, Aβ peptide, Alzheimer's disease, DNA fragmentation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Primary cultures of guinea pig neurons were used as a model system to study the influence of the protein phosphatase inhibitor okadaic acid (OA) on the secretion, processing and phosphorylation of the amyloid precursor protein (APP). This primary cell culture system mimics more closely than other cell culture systems the human in vivo condition, as guinea pig APP is 98% homologous to human APP at the protein level, identical regarding the Aβ sequence and is processed in a similar manner as human APP. Both intracellular and secreted APP was upregulated by OA treatment (0.3 nM–10 nM) of 14 days old cultures in a concentration dependent manner while the amount of Aβ in the medium was decreased. OA treatment did not affect cell membrane integrity of primary neurons but induced DNA fragmentation. Phosphorylation of APP was unchanged by the low OA concentration used. These results show that OA treatment of guinea pig primary cultures might be used as a model to study the effects of modulation of signal transduction on secretion and processing of APP.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1435-1463
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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