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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 60 (1983), S. 175-182 
    ISSN: 1432-0533
    Keywords: Pick's disease ; Pick bodies ; Neurofibrillary tangles ; Neurofilaments ; Monoclonal antibodies ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We used rabbit antisera to the 210,000; 155,000; and 70,000 mol. wt. neurofilament — polypeptides and monoclonal antibodies (BF 10; RT 97) known to react with human neurofilaments in an immunohistochemical study of neuronal changes in Pick's disease and in senile dementia of the Alzheimer type. Pick bodies as well as neurofibrillary tangles and neurites showed strong reactivity with the monoclonal antibodies but remained unlabeled when treated with the rabbit polyclonal antisera. Our results indicate that the stained material in Pick bodies share antigenic determinants with neurofibrillary tangles and neurofilaments.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0533
    Keywords: Progressive supranuclear palsy ; Alzheimer's disease ; Neurofibrillary tangles ; Abnormal neurites ; Tau protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Light microscopic immunohistochemical investigations were performed on neurofibrillary tangles (NFT) in four histologically confirmed cases of Alzheimer's disease (AD) and in five patients with a progressive supranuclear palsy (PSP). The antibody panel included antisera to the neuronal microtubule-associated protein, tau, and to isolated paired helical filaments (PHF), as well as mouse monoclonal antibodies (MAbs) to phosphorylated epitopes on high and medium molecular weight neurofilament subunits (RT97 and BF10, respectively). Paraffin sections were also impregnated with the Gallyas silver method, which specifically stains tangles and cortical neuropil threads in AD, but does not stain normal neurofilaments. All tangles in PSP and AD showed consistent immunostaining with antibodies to tau protein and isolated PHF, regardless of their localization. MAbs RT97 and BF10, however, did not stain or only weakly stained, subcortical tangles in PSP and AD, whereas most cortical NFT in AD were intensely immunostained. All tangles in PSP were as heavily impregnated with Gallyas as they were in AD. Furthermore there were extensive networks of Gallyaspositive, tau- and PHF-immunoreactive neurites in subcortical gray areas containing NFT, and bundles of positive axons in white matter tracts interconnecting subcortical nuclei of PSP. Our studies indicate a much more extensive disruption of fibrillar proteins in PSP subcortical neurons than previously reported. They furthermore indicate a very similar antigenic profile of NFT in PSP and AD, as far as subcortical neurons are concerned.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0533
    Keywords: Lewy bodies ; Pale bodies ; Substantia nigra ; Parkinson's disease-Ubiquitin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prevalance of pale bodies and Lewy bodies was studied in the substantia nigra of 12 patients with typical Parkinson's disease (PD), in 5 patients with diffuse Lewy body disease (DLBD), and in a group of neurologically normal controls. Anti-ubiquitin antibodies labelled pale bodies and Lewy bodies in typical PD and DLBD, and there was a strong positive correlation between numbers of ubiquitin-immunoreactive pale bodies and Lewy bodies. BF10, a monoclonal antibody against a phosphate-dependent epitope of neurofilament 155-kDa polypeptide subunit, immunolabelled 57% of Lewy bodies and 15% of pale bodies in typical PD. Some pale bodies and Lewy bodies were seen in the substantia nigra of 2 of 5 neurologically normal, aged controls, probably representing “incidental PD”. We conclude that there is a close relationship between pale bodies and typical Lewy bodies in the substantia nigra in clinical varicties of PD, and that these inclusions share antigenic determinants. If pale bodies and Lewy bodies reflect separate aspects of the cellular pathology in PD, their formation probably occurs in parallel. Alternatively, these observations may suggest that pale bodies represent a stage in the formation of Lewy bodies.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0533
    Keywords: Senile dementia of Alzheimer type ; Pick's disease ; Monoclonal antibodies ; Pick bodies ; Alzheimer neurofibrillary tangles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Section of formaldehyde-fixed paraffinembedded cortical and hippocampal brain tissue from five cases with senile dementia of Alzheimer type (SDAT) and five cases with Pick's disease (PD) were immunostained with the monoclonal antibodies (mabs) 147, RT 97, BF 10 and 8D8 with and without pretreatment with alkaline phosphatase (AP) or trypsin (Tr). The mabs 147, RT 97 and BF 10 had previously been demonstrated to bind exclusively to phosphorylated epitopes of neurofilament proteins, while mab 8D8 is shown in this report to bind mainly, but not exclusively, to phosphorylated neurofilament epitopes. The mabs RT 97, BF 10 and 8D8, but not 147 stain most, if not all, Pick bodies (PB) and Alzheimer neurofibrillary tangles (NFT). When sections are pretreated with AP or Tr the immunostaining with mab BF 10 is very resistent in both PB and NFT. This resistance of PB and NFT is in contrast to the reduced staining of axons and of swollen cells in PD by the same enzymatic pretreatment. Immunostaining with mab RT 97 of PB and NFT is reduced moderately by AP and considerably by Tr. Only when stained with mab 8D8 is there a discrepancy between PB and NFT in their reaction to the pretreatment with AP: NFT staining with mab 8D8 is not affected, while that of PB is abolished. Thus, in spite of their different ultrastructure, PB and NFT are very similar immunocytochemically and in the accessibility of their phosphorylated epitopes to enzymatic treatment.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0533
    Keywords: Senile plaque ; Paired helical filaments ; Microtubule-associated (MAP)-tau protein ; Neurofibrillary tangles ; Alzheimer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Although much work has been directed recently towards unravelling the protein chemistry of neurofibrillary tangle (NFT) and senile plaque (SP) components in Alzheimer's disease, the pathogeneses of these lesions remains largely unknown and the problem of their relationship is unresolved. In particular, although paired helical filaments (PHF) have long been documented in SP neurites, we do not know if they are of pathogenetic relevance for the formation of the SP. To investigate the relationship between NFT and SP, we examined antigenic properties of proteins in SP neurites in neocortical tissues of patients with senile dementia of Alzheimer type, in the presence or absence of NFT in the same cortical area. We used two polyclonal antibodies directed against PHF and microtubule-associated protein (MAP)-tau and three monoclonal antibodies (MAbs) (RT97, BF10, 147) to phosphorylated epitopes of human neurofilament polypeptides, as well as the Gallyas silver impregnation method which specifically stains PHF in NFT and neurites. The main finding of our investigations consists in a differential pattern of immunoreactivity of SP neurites depending on the presence or absence of NFT in the neocortex. In the presence of NFT, there were numerous neuropil threads and SP neurites containing Gallyas-positive, as well as anti-PHF- and anti-tau-labelled material. In the absence of NFT in the neocortex there was a striking absence of any Gallyas-positive or PHF- and tau-immunoreactive structure in the cortical neuropil and in SP neurites, irrespective of the maturation stage of the SP. In contrast with these results, the number of neurites labelled by MAbs RT97, BF10 and 147 in SP and in the neuropil was apparently unaffected by the presence or absence of NFT. Amyloid in SP, remained consistently unstained by all antibodies of the panel as well as by the Gallyas stain. Our findings indicate that PHF and tau polypeptides are facultative components of SP neurites and suggest that the development of SP may occur independently of PHF pathology in neocortical neurons.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0533
    Keywords: Lewy bodies ; Pale bodies ; Neurofibrillary tangles ; Pick bodies ; Globose tangles ; Ubiquitin ; Antibodies ; Immunocytochemistry ; Alzheimer's disease ; Parkinson's disease ; Pick's disease ; Progressive supranuclear palsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ubiquitin has previously been identified as a component of neuronal inclusions in neurodegenerative disorders. In this investigation, we examined tissue from cases of Alzheimer's disease (AD), Pick's discase, Parkinson's disease (PD), and progressive supranuclear palsy (PSP) to identify previously unrecognized ubiquitinated structures and to assess the evolution of neuronal inclusions. In AD, approximately 60% of neurofibrillary tangles (NFTs) that were stained with an anti-paired helical filaments (PHF) serum were identified by the ubiquitin antibodies. Extracellular NFTs were not labelled with anti-PHF but were unlabelled or weakly labelled with anti-ubiquitin antibodies. In Pick's disease, most Pick bodies were strongly labelled by the ubiquitin antibodies, and in addition some hippocampal CA1 neurones contained granular or strand-like ubiquitin-immunoreactive (IR) inclusions associated with more typical Pick bodies. Typical Lewy bodies in PD cases showed an unlabelled central core with an outer ring intensely labelled by ubiquitin antibodies. Pale bodies in pigmented substantia nigra neurones appeared as large well-defined, rounded structures without an identifiable core or peripheral zone. Some pale bodies were unlabelled by ubiquitin antibodies, but others showed labelling of variable intensity. Pale bodies which were labelled by ubiquitin antibodies tended also to be labelled by BF10, a monoclonal antibody against phosphorylated neurofilaments. We suggest that pale bodies in PD may represent stages in the formation of Lewy bodies. In addition, we observed numerous spindle-shaped ubiquitin-IR swellings of dendrites of pigmented substantia nigra neurones. In contrast to inclusions of AD and Pick's disease, the PHF-positive fibrillary neuronal inclusions of PSP were either unlabelled or only weakly labelled by ubiquitin antibodies. No ubiquitinated structures were seen in neurones from corresponding areas in aged controls. Identification of ubiquitinated proteins in neurodegenerative disorders may provide insights into molecular events associated with cell death.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 64 (1986), S. 103-114 
    ISSN: 1432-1440
    Keywords: Alzheimer's disease ; Dementia ; Cytoskeleton ; Pathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The most important morphological findings in dementia of Alzheimer type (DAT) are Alzheimer neurofibrillary tangles, senile plaques, amyloid angiopathy, granulovacuolar degeneration and Hirano bodies. The morphological and immunocytochemical findings in these changes are described, in particular those related to the pathological cytoskeleton. Their possible relationship to the disturbed synthesis of neurotransmitters recently demonstrated is considered, and their relevance for the clinical syndrome of dementia is discussed. Hypothetical etiologies (ageing per se, genetics, infection and chronic intoxication) are briefly mentioned.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Cytoplasmic inclusion bodies that are accumulations of neurofilaments are the pathological hallmark of many neurodegenerative diseases and have been produced in transgenic mice by overexpression of mouse (NF-L and NF-M; light and medium chains, respectively) and human (NF-M and NF-H; medium and heavy chains, respectively) neurofilament subunits. This report describes a neuronal culture model in which human NF-L was overexpressed to produce cytoplasmic accumulations of neurofilaments within cell bodies concomitant with the collapse of the endogenous neurofilament network. Electron microscopy showed that, within accumulations, neurofilaments retained a filamentous structure. The culture model thus provides a novel system in which the effect on neurofilament accumulations of manipulating protein phosphorylation can be studied. Treatment of cells containing neurofilament accumulations with bisindolylmaleimide, a specific protein kinase C inhibitor, resulted in regeneration of the filamentous network; this effect was not due to a change in the level of transfected NF-L expression. These findings lend support to the suggestion that an impairment in the regulation of protein phosphorylation may lead to the accumulation of neurofilaments seen in neurodegenerative disease.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 455 (1985), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 1 (1989), S. 9-9 
    ISSN: 1435-1463
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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