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  • 1
    ISSN: 1432-0533
    Keywords: Apolipoprotein E ; Dementia ; Diffuse Lewy body disease ; Alzheimer's disease ; Parkinson's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Apolipoprotein E (APOE) is a lipoprotein expressed in liver and brain as one of three isoforms (APOE 2, APOE 3 and APOE 4). Recent findings suggest that the presence of APOE 4 is associated with an increased risk for both familial Alzheimer's disease and late-onset Alzheimer's disease. We extended these observations by determining the frequency of APOE alleles in patients with pathologically confirmed Alzheimer's Disease (AD), Parkinson's disease (PD), diffuse Lewy Body disease (DLBD), AD with concomitant PD pathology, demented PD patients without or with concomitant AD pathology and in schizophrenics with a progressive dementia (SCHIZ+DEM). The APOE genotype was determined by restriction digestion of polymerase chain reaction-amplified DNA isolated from frozen brain samples. The frequency of the APOE ɛ4 allele was highest among sporadic AD and DLBD patients (0.30 and 0.38, respectively) and lowest in the SCHIZ+DEM and non-demented PD patients (0.06 and 0.1, respectively). Thus, the APOE ɛ4 allele is over-represented selectively in patients with dementias associated with plaques and tangles and/or cortical Lewy bodies, but not in demented schizophrenics or non-demented PD patients.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0533
    Keywords: Key words Apolipoprotein E ; Dementia ; Diffuse Lewy body disease ; Alzheimer's disease ; Parkinson's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Apolipoprotein E (APOE) is a lipoprotein expressed in liver and brain as one of three isoforms (APOE 2, APOE 3 and APOE 4). Recent findings suggest that the presence of APOE 4 is associated with an increased risk for both familial Alzheimer's disease and late-onset Alzheimer's disease. We extended these observations by determining the frequency of APOE alleles in patients with pathologically confirmed Alzheimer's Disease (AD), Parkinson's disease (PD), diffuse Lewy Body disease (DLBD), AD with concomitant PD pathology, demented PD patients without or with concomitant AD pathology and in schizophrenics with a progressive dementia (SCHIZ+DEM). The APOE genotype was determined by restriction digestion of polymerase chain reaction-amplified DNA isolated from frozen brain samples. The frequency of the APOE ε4 allele was highest among sporadic AD and DLBD patients (0.30 and 0.38, respectively) and lowest in the SCHIZ+DEM and non-demented PD patients (0.06 and 0.1, respectively). Thus, the APOE ε4 allele is over-represented selectively in patients with dementias associated with plaques and tangles and/or cortical Lewy bodies, but not in demented schizophrenics or non-demented PD patients.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0533
    Keywords: Key words Vimentin ; Neurofibrillary tangle ; Subiculum ; Orbitofrontal cortex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clinical and neuropsychological studies of chronically institutionalized patients with schizophrenia indicate that severe cognitive impairment and functional disability in late life are very prevalent. The biological substrates for this dementia remain unknown. While subtle cytoarchitectural and morphometric abnormalities have been described in patients with schizophrenia and interpreted as reflecting aberrant neurodevelopment, post-maturational injury or neurodegeneration associated with gliosis remain as plausible explanations of at least some of the clinical manifestations of schizophrenia. We monitored astrocytosis and neurofibrillary tangle (NFT) formation in 21 elderly patients with schizophrenia (14 with concurrent dementia, 7 without), and in 12 normal and 5 Alzheimer's disease (AD) control cases. Astrocytes in ventromedial temporal, frontal, and calcarine cortices were immunohistochemically identified with monoclonal antibodies directed at glial fibrillary acidic protein (GFAP) and vimentin, and NFTs were labeled with an anti-tau antibody specific for paired helical filaments. There were no increases in GFAP- or vimentin-immunoreactive astrocyte counts, GFAP optical density, or NFT counts for the schizophrenic group as a whole compared to the non-neuropsychiatric group, while both groups differed from AD. When patients with schizophrenia were divided into demented and non-demented subtypes, those with dementia demonstrated significantly greater numbers of GFAP-positive astrocytes than those without dementia. These data may reflect an up-regulation of GFAP in normal astrocytes or the presence of reactive astrocytosis in a subgroup of schizophrenics. In the absence of any diagnostic neuropathological findings in this subgroup, the implications of these observations for the pathogenesis of schizophrenia remain to be determined.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 92 (1996), S. 217-231 
    ISSN: 1432-0533
    Keywords: Key words Neuropathology ; Schizophrenia ; Postmortem ; Neurodevelopment ; Neurdegenerative
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The search for the defining neuropathology of schizophrenia continues to be one of the highest priority areas of research into this severely debilitating and common neuropsychiatric disorder. While lesions that are diagnostic of the disorder have not yet been identified, recent efforts employing molecule-specific probes and quantitative methods of analysis have enumerated many potentially important findings in the brains of patients with schizophrenia that warrant confirmation and elucidation. In this review, the major findings of six broad areas of neuropathological investigation are summarized and discussed. While substantial controversy exists in all areas, in sum: (1) diagnostic neuropathological investigations find only assorted and nonspecific abnormalities in the brains of schizophrenics that are likely to be representative of lesions found in age-compatible control groups; (2) morphometric studies of gross structures generally confirm the clinical in vivo neuroimaging findings of enlarged ventricles, decreased size of ventromedial temporal lobe structures, and decreased parahippocampal cortical thickness; (3) morphometric microscopy studies find frequent alterations in neuron density and decreased neuron size in limbic, temporal, and frontal regions; (4) investigations of connectivity are at an early stage but describe abnormal dendritic spine densities in the cortex, various changes in synaptic vesicle protein expression in limbic, temporal, and frontal cortices, and alterations in glutamatergic, catecholaminergic, and intrinsic innervation in anterior cingulate cortex – together, these findings suggest a “miswiring” in the schizophrenic brain; (5) investigations of aberrant neurodevelopment in schizophrenia describe abnormalities in cortical cytoarchitecture and several developmentally regulated proteins in the hippocampal region suggesting abnormal neuronal migration, differentiation, and/or cell pruning; and (6) studies of neurodegeneration and neural injury find a general lack of neurodegenerative disease lesions or ongoing astrocytosis that would indicate post-maturational neural injury.
    Type of Medium: Electronic Resource
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