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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 81 (1991), S. 588-590 
    ISSN: 1432-0533
    Keywords: Alzheimer disease ; Amyloid ; Phagocytosis ; Microglia ; beta protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunocytochemistry using monoclonal antibodies to β/A4 protein was applied to study the macrophages involved in the removal of amyloid deposits. The material examined included necrotic brain tissue areas with abundant amyloid deposits collected from 32 autopsy cases. The β/A4-immunoreactive products were found in numerous macrophages, appearing as early as 24 h after the onset of stroke. Immunogold electron microscope studies allowed us to localize the reaction product to the secondary lysosomes. Our study clearly demonstrates the differences between macrophages engaged in amyloid removal and microglial cells associated with amyloid deposits, which according to previous observations contain β/A4 material within endoplasmic reticular channels.
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  • 2
    ISSN: 1432-0533
    Keywords: Alzheimer's disease ; Tissue culture ; Microglia ; Amyloid ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The function of microglia associated with β-amyloid deposits still remains a controversial issue. On the basis of recent ultrastructural data, microglia were postulated to be cells that form amyloid fibrils, not phagocytes that remove amyloid deposits. In this electron microscopic study, we examined the ability of microglia to ingest and digest exogenous amyloid fibrils in vitro. We demonstrate that amyloid fibrils are ingested by cultured microglial cells and collected and stored in phagosomes. The ingested, nondegraded amyloid remains within phagosomes for up to 20 days, suggesting a very limited effectiveness of microglia in degrading β-amyloid fibrils. On the other hand, we showed that in microglial cells of classical plaques in brain cortex of patients with Alzheimer's disease, amyloid fibrils appear first in altered endoplasmic reticulum and deep infoldings of cell membranes. These differences in intracellular distribution of amyloid fibrils in microglial cells support our observations that microglial cells associated with amyloid plaques are engaged in production of amyloid, but not in phagocytosis.
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  • 3
    ISSN: 1432-0533
    Keywords: Alzheimer's disease ; Neuropathology ; Mental retardation ; Amyloid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The densities of neurofibrillary tangles (NFT) and neuritic plaques (NP) were assessed quantitatively in the brains of 303 mentally retarded adults 23 to 90 years of age at the time of their deaths (mean=59.5 years). Cases with Down's syndrome, hydrocephalus and metabolic disorders were excluded from the study. Examinations of frontal, temporal, parietal, and occipital cortex, as well as hippocampus and parahippocampal gyrus were made in every case. NPs and/or NFTs were observed within the brains of 163 cases (53.8%). Detailed analyses indicated that NP density within all brain regions examined was positively related to age, with the largest age associated increases in density seen in frontal and temporal regions. In contrast, NFT density increased with age only within hippocampus and parahippocampal gyrus, but not neocortex. In addition, NP lesions within neocortex were more diffusely distributed across regions for older compared to younger cases, while no similar age-associated change in the topography of NFTs was observed. Finally, factor analyses of the combined NP and NFT data indicated that, while strong correlations existed across the various brain regions for measures of NP and NFT densities, considered separately, there was virtually no indication of regional associations between these two types of lesions. While these data, from cases with mental retardation, cannot be generalized directly to the nonretarded population, they provide strong evidence that models of Alzheimer pathogenesis must take into account the fact that regional densities of NPs and NFTs, and, therefore, the underlying processes associated with formation of these lesions, can be largely independent.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0533
    Keywords: Alzheimer's disease ; Amyloid ; Immunocytochemistry ; Neuritic plaques ; Paired helical filaments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunocytochemistry with monoclonal antibodies to the β-protein and to antigens associated with paired helical filaments (PHF) allows us to selectively stain two major components of neuritic (senile) plaques (NP): PHF and amyloid deposits. Using this method, the structure of NP in the brains of Alzheimer disease victims was compared to their structure in the brains of non-demented aged individuals selected for high numbers of NP. It is demonstrated that the dystrophic neurites participating in the plaque formation contain PHF only when cortical nerve cells in the same brain area form neurofibrillary tangles (NFT). People with many NP and many NFT were always demented, whereas people with many NP but few, if any NFT were not. It is speculated that there is individual susceptibility to the formation of PHF and that their appearance may represent a nonspecific response of the neuronal network to different kinds of injuries, like the deposition of amyloid in Alzheimer disease, or other pathogenic factors associated with various dementive neurodegenerative diseases. It is hypothesized that the deposition of brain amyloid in people resistant to neurofibrillary pathology may induced too little dysfunction for the development of dementia.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 85 (1993), S. 586-595 
    ISSN: 1432-0533
    Keywords: Alzheimer's disease ; Perivascular cells ; Microglia ; Plaques ; Amyloid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Our recent ultrastructural studies of amyloid angiopathy in biopsy specimens from Alzheimer's disease patients showed that perivascular cells and perivascular microglia are involved in the production of amyloid fibrils. Further examination of the walls of the vessels with and without amyloid deposits presented in this report reveals numerous mononuclear cells with a broad spectrum of morphological appearances. Some of these cells produce amyloid in the vascular wall and migrate into the neuropil. Others do not produce amyloid in this location but also migrate through the vascular basal lamina and position themselves on the external surface of basal lamina or in the neuropil outside the vascular astrocytic end-feet processes. The presence of clusters or rows of six or more of these cells in the position of perivascular microglial cells suggests their proliferation in the perivascular region. After leaving the perimeter of the vessel wall, perivascular cells become the perivascular, neuropil, and satellite microglia cells. Migrating perivascular cells become the microglia, which are engaged in amyloid fibril formation and development of classical and primitive plaques.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 54 (1981), S. 63-74 
    ISSN: 1432-0533
    Keywords: Scrapie ; Fibrils ; Amyloid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Abnormal fibrillary structures, designated “scrapie-associated fibrils” (SAF), have been observed using negative stain techniques in subfractions of brains from scrapie-affected animals. SAF have been observed in all combinations of strain of scrapie agent and strain or species of host examined, regardless of their histopathology, in particular the presence or absence of amyloid plaques. SAF consist either of two or four filaments. They are morphologically dissimilar to the normal brain fibrils — microtubules, neurofilaments, glial filaments, and F actin. However, SAF do bear a resemblance to amyloid.
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  • 7
    ISSN: 1432-0533
    Keywords: Scrapie ; Macrophage ; Microglia ; Amyloid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have isolated and characterized a population of brain macrophages from normal and scrapieinfected mice. The cells are phagocytic, possess Fc-IgG receptors, Mac-1 surface antigen and proliferate in the presence of macrophage colony stimulating factor. They resemble microglia in that they have a plasmalemmal distribution of the enzyme nucleoside diphosphatase, a property that is characteristic of microglia in situ. In two of the three combinations of scrapie agent and mouse strain examined, the number of brain macrophages was several fold higher than in normal control mice. The increase was not observed in mice infected intraperitoneally or in control mice inoculated with normal brain homogenate. The increase is detectable as early as 3–5 weeks postinoculation. The agent/host combination that failed to show an increase in brain macrophages is one that develops large numbers of amyloid plaques. These observations suggest that these cells are closely associated with the scrapie pathogenic process in the CNS. The failure of these cells to increase in the plaque forming model of scrapie disease also suggests that they play a role in the control of CNS amyloidogenesis.
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  • 8
    ISSN: 1432-0533
    Keywords: Amyloid ; Alzheimers disease ; Scrapie ; EM ; Isolation ; Gerstmann-Sträussler syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The structure of partially purified, CNS amyloid fibrils from three different sources have been compared by negative stain EM. The fibrils isolated from brains with senile dementia of Alzheimer type were 4–8 nm in diameter, narrowing every 30–40 nm and apparently composed of two 2–4 nm filaments. The fibrils from a Gerstmann-Sträussler syndrome brain were 7–9 nm in diameter, narrowing every 70–80 nm and with a suggestion that they are composed of two 3–5 nm filaments. The fibrils isolated from 87V scrapie-affected mouse brains were 4–8 nm in diameter with a twist every 15–25 nm presumably composed of two 2–4 nm filaments. The fibrils from the scrapie brains were usually observed in pairs. The shape of the clusters of the isolated amyloid fibrils observed in each disease was similar in negative stain and thin section EM preparations and was related to the characteristic morphology of the amyloid fibrils in the neuritic and amyloid plaques in situ. The structural differences between the CNS amyloid fibrils from the various diseases studied by us may reflect differences in the polypeptides which comprise the fibril and/or a different pathogenesis in the formation of the amyloid fibrils.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 73 (1987), S. 1-11 
    ISSN: 1432-0533
    Keywords: Alzheimer's disease ; Neuritic plaques ; Amyloid ; Neurofibrillary tangles ; Lectin receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Biotinyl derivatives of several lectins and avidin-horseradish peroxidase were used to study the localization of glycoconjugates in amyloid plaques and in neuritic tangles in brains of patients with Alzheimer's disease (AD), Downs syndrome (DS) and Gerstmann-Sträussler syndrome (GSS). The lectins tested recognize the following residues: β-d-galactosyl [Ricinus communis agglutinin 120, (RCA-1) and peanut agglutinin, (PNA)]; α-d-galactosyl [Griffonia simplicifolia agglutinin (GSA)]; α-d-mannosyl〉α-d-glucosyl [concanavalin A (Con A) andLens culinaris agglutinin (LcH)];N-acetyl- andN-glycolylneuraminic acid [Limax flavus agglutinin (LFA) andLimulus polyphemus agglutinin (LPA)];N-acetyl-glucosaminyl and sialyl [wheat germ agglutinin (WGA)];N-acetyl-d-galactosaminyl [Helix pomatia agglutinin (HPA) andDolichos biflorus agglutinin (DBA)] and α-l-fucosyl [Ulex europeus agglutinin (UEA-1)]. The majority of lectins listed above bind preferentially to the peripheral area of AD plaques, whereas in plaques of DS they are mainly bound to central amyloid core. In neurofibrillary tangles of AD brains only residues recognized by WGA and HPA or DBA were found, whereas in DS brains, in addition to above mentioned, β-d-galactose (RCA-1) and sialic acid (LFA) were also present. In brain microblood vessels the strongest reaction in endothelia appeared with UEA-1 and RCA-1, indicating the abundance of α-l-fucosyl and β-d-galactosyl residues. In AD brains deposits of amyloid were noted in the wall of some blood vessels, where monosaccharide residues recognized by RCA-1, GSA, UEA and WGA but not by Con A and LFA were present. However, our studies of some organs (liver, kidney, heart and testes) of patients with generalized amyloidosis revealed a lack of these sugar residues. It indicates, that the composition of amyloid present in brains of AD is different to that in other organs in generalized amyloidosis.
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