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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 48 (1987), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Indices of presynaptic serotonergic nerve endings were assayed in neocortical biopsy samples from patients with histologically verified Alzheimer's disease. The concentrations of 5-hydroxytryptamine (serotonin) and 5-hydroxyindoleacetic acid, serotonin uptake, and K+-stimulated release of endogenous serotonin were all found to be reduced below control values. Changes occurred in samples from both the frontal and temporal lobes, but they were most severe (at least a 55% reduction) in the temporal lobe. This is indicative of substantial serotonergic denervation. Values for serotonergic markers in Alzheimer's disease samples did not show correlations with rating of the severity of dementia, indices of cholinergic innervation, or senile plaque and cortical pyramidal neurone loss. However, neuronbrillary tangle count and an index of glucose oxidation (both probably reflecting pyramidal cells) correlated with the concentration of 5-hydroxyindoleacetic acid.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Frame-shifted amyloid precursor protein (APP+1), which has a truncated out-of-frame C-terminus, accumulates in the neuropathological hallmarks of patients with Alzheimer's disease pathology. To study a possible involvement of APP+1 in the pathogenesis of Alzheimer's disease, we expressed APP695 and APP+1 in the HEK293 cell-line and studied whether the processing of APP695 was affected. APP+1 is a secretory protein, but high expression of APP695 and APP+1 results in the formation of intracellular aggregate-like structures containing both proteins and Fe65, an adaptor protein that interacts with APP695. APP+1 is shown to interact with APP695, suggesting that these structures consist of functional protein complexes. Such an interaction can also be anticipated in post-mortem brains of young Down's syndrome patients without any sign of neuropathology. Here we observed APP+1 immunoreactivity in beaded fibres. Additional support for functional consequences on the processing of APP695 comes from a 1.4-fold increase in levels of secreted amyloid β40 in cells co-expressing APP695 and APP+1, although APP+1 itself does not contain the amyloid β sequence. Taken together, these data show that co-expression of APP695 and APP+1 affects the processing of APP695 in a pro-amyloidogenic way and this could gradually contribute to Alzheimer's disease pathology, as has been implicated in Down's syndrome patients.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Histopathology 13 (1988), S. 0 
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The neuropathology of Down's syndrome at middle age is compared with that of Alzheimer's disease at that age, through a review of the published literature and from the author's personal observations. The pathological changes of Down's syndrome at middle age, i.e. the form and distribution of senile plaques and neurofibrillary tangles, and the pattern of involvement (atrophy) of neuronal systems are qualitatively the same as those of Alzheimer's disease at that age. Quantitative differences do occur and these may relate to biological or sociological variations inherent to the two parent populations. It is concluded that, in pathological terms, patients with Down's syndrome at middle age do indeed have Alzheimer's disease. Some ways in which a study of patients with Down's syndrome can give insight into the nature and development of the pathological changes of Alzheimer's disease are put forward and discussed.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0533
    Keywords: Cerebellum ; Cerebral cortex ; Amyloid ; Alzheimer's disease ; Down's syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The extent of amyloid deposition within the cerebellum and the cerebral cortex was assessed and compared, using anti-amyloid protein (A4) immunostaining and a novel methenamine silver method, in 20 patients aged between 60 and 77 years with Alzheimer's disease (AD), 29 patients aged between 13 and 71 years with Down's syndrome (DS), 26 demented patients with disorders other than AD and DS and in 20 non-demented elderly individuals of age range 60–102 years. In AD, amyloid deposits were noted in the cerebellar cortex in 90% of patients and in the meningeal vessels of the cerebellum in 80% of patients. In DS, amyloid deposits were seen in the cerebellar cortex in 82% of patients over 30 years of age and was universal in patients over 50 years of age. Overall, in DS, amyloid deposits were present in the meningeal vessels of the cerebellum in 79% of patients, but were present in 94% of those patients over 50 years of age. The sites of amyloid deposition in the cerebellar cortex were (poorly) detected by lectin histochemistry (Concanavalin A binding) in only 40% of patients with AD and 43% of all patients with DS (69% of those over 50 years of age). No amyloid deposits were seen in either the cerebellar cortex or its meningeal vessels in any of the 20 non-demented elderly individuals nor in any of the non-Alzheimer demented patients. The cerebellar amyloid deposits were never associated with a neuritic change [i.e. as characterised by the presence of (taupositive) paired helical filaments (PHF)] and neurofibrillary tangles were seen only in a few cells of the dentate nucleus in a single patient with AD and in three of the elderly DS patients. Amyloid deposits were numerous in the cerebral cortex of all patients with AD and in all, except the 13-year-old patient, with DS. In all the AD patients and in most of the DS patients over 30 years of age, many of the cerebral cortical amyloid deposits were associated with neurites and were strongly recognised by lectin histochemistry. Amyloid deposits were present within the meningeal vessels of the cerebral cortex in 75% patients with AD and 72% of patients, over 30 years of age, with DS (82% of those over 50 years of age). These data indicate that the process of amyloidosis in AD and in elderly DS patients is not restricted to the cerebral cortex and may affect other grey matter regions, particularly the cerebellum. However, it seems to be only in the cerebral cortex that such deposits are widely associated with a ‘reactive’ neuritic (PHF) change and an accumulation of saccharide. It is probably these latter alterations that mark the process of neuronal (neurofibrillary) degeneration that leads to functional deficits.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 85 (1993), S. 334-340 
    ISSN: 1432-0533
    Keywords: Brain atrophy ; Frontal lobe dementia ; Pick's disease ; Frontal lobe dementia with motor neurone disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The topographic distribution of brain atrophy was quantified by image analysis of fixed brain slices from ten patients dying with dementia of frontal type (DFT) and from six other patients dying with dementia of frontal type with motor neurone disease (DFT+MND). In both groups the atrophy was maximal within frontal, anterior temporal and anterior parietal regions of cortex, although other structures such as the amygdala, caudate nucleus, thalamus and hippocampus were also affected. The magnitude of the atrophy was much greater, in all affected regions, in DFT alone than in DFT+MND. Grey and white matter were affected equally in DFT alone although in DFT+MND a preferential white matter involvement was noted. No differences in the topographic distribution of the atrophy was observed in cases of DFT showing a spongiform degeneration of the cortex compared to those showing a gliotic degeneration with, or without, Pick cells and Pick bodies.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0533
    Keywords: Key words Alzheimer's disease ; Amyloid precursor protein ; Pyramidal neurones ; mRNA ; Choline acetyltransferase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Post-mortem cerebral cortex from 15 demented patients was specially collected to minimise autolysis and two membrane fractions and one soluble fraction were quantitatively examined for the major species of β-amyloid precursor protein (APP) of high apparent molecular mass (≥ 80 kDa) together with the major mRNA species encoding APP isoforms. The number of pyramidal neurones and astrocytes, putative biochemical indices of interneurones and pyramidal neurones, and choline acetyl transferase activity were also determined. Multiple regression analysis has been used to investigate intercorrelations of APP species with biochemical and morphometric measures, free of any effects of confounding demographic variables. Subjects with Alzheimer's disease showed a loss of cholinergic activity and D-aspartate uptake compared with patients with other causes of dementia. The major finding of the study is that measures of neurones rather than astrocytes most closely correlate with the concentration of APP. Pyramidal cell numbers were positively correlated with mRNA for APP695. APP in the soluble fraction showed a negative correlation with pyramidal cell numbers and cholinergic activity. These results indicate that neurones within the cerebral cortex are the major source of APP, and that secretion of APP is dependent upon cortical pyramidal neuronal activity and cholinergic activity.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0533
    Keywords: Alzheimer's disease ; Amyloid precursor protein ; Pyramidal neurones ; mRNA ; Choline acetyltransferase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Post-mortem cerebral cortex from 15 demented patients was specially collected to minimise autolysis and two membrane fractions and one soluble fraction were quantitatively examined for the major species of β-amyloid precursor protein (APP) of high apparent molecular mass (≥ 80 kDa) together with the major mRNA species encoding APP isoforms. The number of pyramidal neurones and astrocytes, putative biochemical indices of interneurones and pyramidal neurones, and choline acetyl transferase activity were also determined. Multiple regression analysis has been used to investigate intercorrelations of APP species with biochemical and morphometric measures, free of any effects of confounding demographic variables. Subjects with Alzheimer's disease showed a loss of cholinergic activity and d-aspartate uptake compared with patients with other causes of dementia. The major finding of the study is that measures of neurones rather than astrocytes most closely correlate with the concentration of APP. Pyramidal cell numbers were positively correlated with mRNA for APP695. APP in the soluble fraction showed a negative correlation with pyramidal cell numbers and cholinergic activity. These results indicate that neurones within the cerebral cortex are the major source of APP, and that secretion of APP is dependent upon cortical pyramidal neuronal activity and cholinergic activity.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0533
    Keywords: Key words Amyloid β-protein ; Alzheimer’s disease ; Monoclonal antibodies ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have used the end-specific monoclonal antibodies to amyloid β-protein (Aβ), BC05 and BA27, to investigate the molecular characteristics of the cored or stellate type of amyloid plaque that is sometimes present, along with the more common diffuse type of plaque, in the cerebellar cortex in (usually younger) cases of Alzheimer’s disease. In five such cases of Alzheimer’s disease the (many) cored plaques were strongly BA27, but less strongly BC05, immunopositive, indicating the presence of (much) Aβ40 and Aβ42(43), respectively. Diffuse plaques were only BC05 positive, except on rare occasions where a little BA27 reactivity was present. Cerebellar cored plaques, like the diffuse plaques, were not associated with tau or astrocytic (glial fibrillary acid protein) immunoreactivity, though in contrast to cerebellar diffuse plaques, but like the cored plaques in the cerebral cortex, microglial cells were usually present. The cause of this form of Aβ deposition in the cerebellum is not known. Although congophilic angiopathy was severe in two patients, this was only mild in the others. Similar plaques were also seen in the cerebellum of most, but not all, of five other younger patients with chromosome 14-linked Alzheimer’s disease and again, although congophilic angiopathy was severe in one such case with many cored plaques, this was not so in the others. At present the relationship (if any) between this pathological change and the possession of the chromosome 14 mutation of Alzheimer’s disease or the occurrence of congophilic angiopathy remains uncertain.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 76 (1988), S. 595-598 
    ISSN: 1432-0533
    Keywords: Down's syndrome ; Alzheimer's disease ; Basal ganglia ; Calcification ; Ageing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prevalance and severity of calcification in the basal ganglia (BGC) has been examined histopathologically in 194 patients divided into ten diagnostic categories. The prevalence and severity of BGC was greater (for age) in Down's syndrome and in patients under 75 years of age with Alzheimer's disease. The severity, but not the prevalance, of BGC was greater in Down's syndrome than in patients of similar age with Alzheimer's disease. Both the prevalence and the severity of BGC in patients over 75 years of age with Alzheimer's disease were as expected for age alone. The increased prevalence and severity of BGC in Down's syndrome and in younger patients with Alzheimer's disease appeared not to be related to the presence of dementia or degenerative disease per se, nor was it affected by the presence of cerebral infarction. BGC may result from an age-related disturbance of the structure of arteries within the globus pallidus, which is accelerated (or occurs prematurely) in Down's syndrome and in younger patients with Alzheimer's disease, but probably does not form part of that spectrum of changes that constitutes the pathological basis of Alzheimer's disease.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 78 (1989), S. 551-554 
    ISSN: 1432-0533
    Keywords: Huntington's chorea ; Nucleus basalis ; Locus caeruleus ; Substantia nigra ; Raphe nucleus dorsalis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The number and nucleolar volume of nerve cells within the nucleus basalis of Meynert, locus caeruleus, substantia nigra and dorsal raphe were examined in five patients with Huntington's chorea. No significant changes in nerve cell number were noted in any area in any patient and, although nucleolar volume was reduced in nerve cells of locus caeruleus and substantia nigra in four patients, this was considered to reflect medication rather than to be related to the disease process itself. It is concluded that the subcortical afferent projection systems of the mid-brain and brain stem are unaffected in Huntington's chorea and that the dementia in such patients most likely relates to changes within the cerebral cortex and/or damage to corticopetal pathways within the basal ganglia.
    Type of Medium: Electronic Resource
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