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  • 1
    ISSN: 1435-1463
    Keywords: Keywords: Ageing ; Alzheimer's disease ; degeneration ; neurofilament ; phosphorylation ; tau ; sciatic nerve.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Paired helical filaments containing the microtubule-associated protein tau in an abnormally high phosphorylated state are one of the major hallmarks of Alzheimer's disease. In the central nervous system, this neurofibrillar degeneration preferentially affects long-axon projection neurons. In the peripheral nervous system largely made up by long-axon neurons, formation of paired helical filaments, however, has only rarely been described. In the present study, we have analysed alterations in the content and phosphorylation state of tau and neurofilament protein in the sciatic nerve during ageing and in Alzheimer's disease. The amount of both cytoskeletal proteins remained constant during ageing but was significantly reduced in Alzheimer's disease. The phosphorylation state of tau protein was elevated during ageing as well as in Alzheimer's disease. No indications of a paired helical filament-like aggregation of tau were found. It is concluded that during normal ageing and in Alzheimer's disease, processes are activated in the peripheral nervous system that induce a hyperphosphorylation of tau. Increased phosphorylation of tau in peripheral neurons, however, is not necessarily accompanied by the formation of paired helical filaments. Analysing principal differences in the expression, posttranslational modification and metabolism of tau between central and peripheral neurons might, therefore, help to get a better insight into the mechanism of paired helical filament formation.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0533
    Keywords: Nucleus basalis of Meynert ; Neuronal loss ; Dementia ; Alzheimer's disease ; Paralysis agitans ; Korsakoff's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The nucleus basalis of Meynert, the major source of cholinergic innervation of the cerebral cortex, was morphometrically investigated in 58 cases of neuropsychiatric disorders and compated to 14 controls. The results demonstrate a loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease (70%), paralysis agitans (77%), and Korsakoff's disease (47%) but no marked reduction of neurons in postencephalitic parkinsonism, Huntington's disease, chronic alcoholism without dementia, schizophrenia and infantile brain damage. Neurons of the three subdivisions of the nucleus basalis of Meynert (the nucleus septi medialis, the nucleus of the diagonal band of Broca and the nucleus basalis Meynert neurons in the substantia innominata) may be affected in a different manner in different patients within a single group homogeneous with respect to the usual clinical and neuropathological diagnostic criteria. Cell loss in the basal forebrain is restricted to the large neurons of the nucleus basalis, the immediately adjacent neurons of the globus pallidus externus not being affected. The selective degeneration of these neurons provides the morphological correlate of the cortical cholinergic deficiency in these neuropathological conditions. The degeneration of this discrete cholinergic neuronal population in several disorders of higher cortical function is probably directly related to the progressive deterioration of memory and cognitive processes in affected patients.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0533
    Keywords: Nucleus basalis of Meynert ; Amyloid ; Neuronal loss ; Alzheimer's disease ; Dementia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The deficiency of the cholinergic cortical projection system arising in the different basal forebrain structures collectively referred to as nucleus basalis of Meynert complex is a constant finding in Alzheimer's disease, a disorder which is neuropathologically characterised by the appearance of three intracerebral formes of twisted β-pleated sheet (amyloid) fibrils, neurofibrillary tangles, amyloid-containing neuritic plaques and congophilic amyloid angiopathy. In the present study the quantitative relationship between these hallmarks of the disease, amyloid deposition and neuronal loss in the cholinergic basal forebrain system, was investigated in ten cases of Alzheimer's disease. Besides a constant involvement of the cerebral cortex and hippocampus, all cases of Alzheimer's disease show a large amount of amyloid in the medial septal nucleus, in the diagonal band nucleus and in the substantia innominata which is correlated with neuronal loss in these areas. These amyloid deposits in the basal forebrain are due to congophilic angiopathy associated with plaques and neurofibrillary tangles. The distribution of amyloid deposition in the basal forebrain is restricted entirely to those neuronal clusters which represent the origin of cholinergic innervation of the cerebral cortex and hippocampus. Immediately adjacent structures are not affected. These findings suggest a pathogenetic role of amyloid deposition in the mechanism of degeneration of the cholingeric basal forebrain system.
    Type of Medium: Electronic Resource
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