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  • 1
    Digitale Medien
    Digitale Medien
    Early-onset dementias: clinical, neuropathological and genetic characteristics (1996)
    Springer
    Acta neuropathologica 91 (1996), S. 451-465 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Alzheimer’s disease ; Clinicopathological ; correlations ; Early-onset dementia ; Genetics ; Pick’s ; disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010050452
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  • 2
    Digitale Medien
    Digitale Medien
    Differential distribution of presenilin-1, Bax, and Bcl-XL in Alzheimer’s disease and frontotemporal dementia (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 141-149 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Apoptosis ; Dementia ; Neurofibrillary ; tangles ; Neuroprotection ; Presenilin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We have previously reported that presenilin-1 (PS-1)-immunoreactive neurons survive in late-onset sporadic Alzheimer’s disease (AD). To examine if this is also the case in other dementing conditions, and if it is associated with changes in the expression of the main apoptosis-related proteins, a quantitative immunocytochemical study of presenilin-1, Bax, and Bcl-XL in the cerebral cortex of non-demented and AD patients, and patients with frontotemporal dementia (FTD) was performed. In non-demented cases, the frequency of neurons showing PS-1 immunoreactivity was 25–60%, Bax immunoreactivity 36–54%, and Bcl-XL immunoreactivity 26–63% depending on the cortical area. The frequency of NFT-free neurons which contained PS-1 or Bax was consistently increased in all of the areas in AD. In FTD cases, the percentage of PS-1-, but not Bax-immunoreactive neurons was increased only in areas displaying a substantial neuronal loss. Conversely, there was no difference in the densities of Bcl-XL-containing neurons among the three diagnosis groups. These data suggest that surviving neurons in affected cortical areas in AD show a high expression of PS-1 and Bax, indicating that these proteins play a key role in the mechanisms of cell death in this disorder. In FTD, neurons containing PS-1 are preserved, further supporting a neuroprotective role for this protein in other neurodegenerative disorders.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010051062
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  • 3
    Digitale Medien
    Digitale Medien
    Clinical validity of Braak neuropathological staging in the oldest-old (2000)
    Springer
    Acta neuropathologica 99 (2000), S. 579-582 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Alzheimer’s disease ; Clinicopathological correlations ; Cognitive impairment ; dementia ; Neurofibrillary tangles
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Several studies have demonstrated a good correlation between clinical severity and Braak’s neuropathological staging in Alzheimer’s disease (AD). However, nonagenarians and centenarians display a different pattern of cortical vulnerability to the neurodegenerative process compared to younger elderly, and it is not known whether correlations between clinical severity and neuropathological stages remain valid in this age group. To address this issue we compared Clinical Dementia Rating scale (CDR) scores and Braak stages in 116 patients over 90 years of age with either no cognitive impairment or very mild to severe AD. There is a strong positive correlation between CDR scores and Braak staging (Spearman coefficient = 0.66; P 〈 0.01). However, neuropathological staging does not distinguish cases with normal cognition (CDR 0) from those with mild cognitive changes (CDR 0.5). Unlike younger cohorts, Braak stages I and II are frequently associated with questionable dementia in this age group. Braak stage III overlaps with all CDR levels and correlates poorly with cognitive function. Braak stages IV or greater are consistently associated with at least mild dementia. Consistent with our previous neuropathological analyses of nonagenarians and centenarians, the present data suggest that the substantial involvement of the hippocampus which characterizes Braak stage IV is a key step in the development of overt clinical signs of dementia in the oldest-old. Moreover, they indicate that Braak staging represents a broad concept of the evolution of neurofibrillary tangles rather than a precise hierarchical model associated with a stepwise deterioration of cognitive abilities near the upper limit of life.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010051163
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  • 4
    Digitale Medien
    Digitale Medien
    Dementia lacking distinctive histopathology: clinicopathological evaluation of 32 cases (1995)
    Springer
    Acta neuropathologica 89 (1995), S. 346-355 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Frontal lobe ; Dementia ; Cerebral cortex ; Clinicopathological correlations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We report the neuropathological findings in 32 patients, aged 46–86 years, with demential lacking distinctive histopathology. All of the patients were classified clinically as having Pick's or atypical Pick's disease, but the routine neuropathological evaluation showed no specific histopathological changes such as Pick bodies, senile plaques, neurofibrillary tangles or Lewy bodies. In 50% of the cases the first symptoms appeared before 65 years of age. However, there were 9 patients with onset in the eighth decade. Positive family history was found only in 6 presenile cases. The retrospective evaluation of the clinical records revealed the consistent presence of “frontal” symptomatology, including loss of personal awareness, inappropriate euphoria and stereotyped behavior. Speech disorders were observed in 80% of the cases, whereas temporospatial disorientation and memory impairment were less frequent. Praxis and gnosis were strikingly preserved in most of the cases. The macroscopic neuropathological examination revealed frontal or temporopolar atrophy in 97% of the cases, while the hippocampus and subcortical structures were relatively spared in the majority of the cases. Histologically, four groups were recognized. Group A showed moderate to severe neuron loss and gliosis in the frontal and/or temporopolar cortex without subcortical involvement. In group B, the neocortical cell loss was widespread, and the striatum and substantia nigra displayed differential degrees of gliosis but no neuron loss. Group C patients showed a lesion distribution comparable to that observed in group B but with severe neuron loss in at least one subcortical region. Four cases formed group D, which was characterized by the preservation of the pyramidal neurons in the neocortex and variable subcortical changes. Despite these differences in the topography of pathological changes, all of the cases shared a similar clinical profile. These findings further demonstrate the epidemiological and neuropathological heterogeneity of dementia lacking distinctive histopathology. Furthermore, they suggest that the same clinical manifestations may correspond to several distinct pathological processes in this condition.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00309628
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  • 5
    Digitale Medien
    Digitale Medien
    Neuropathological changes in the cerebral cortex of 1258 cases from a geriatric hospital: retrospective clinicopathological evaluation of a 10-year autopsy population (1994)
    Springer
    Acta neuropathologica 87 (1994), S. 456-468 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Senile plaques ; Neurofibrillary tangles ; Dementia ; Neocortex ; Clinicopathological correlations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract To examine the neuropathological and clinical characteristics of cerebral aging, we evaluated retrospectively a non-selected autopsy population of 1258 patients from the Geriatric Hospital of the University of Geneva School of Medecine. The prevalence of Alzheimer's disease increased with age below 90 years of age. In the nonagenarians and centenarians, there was a decline in the number of affected cases. The distribution with age of neurofibrillary tangles and senile plaques varied among the cortical areas studied. The CA1 field of the hippocampus and the inferior temporal cortex displayed increasing densities of neurofibrillary tangles with age, whereas the superior frontal and the occipital cortex were relatively spared, especially in patients in their tenth and eleventh decade. The percentage of cases presenting with senile plaques in the neocortex and hippocampal structure increased with age with a marked predominance of cases with moderate to high senile plaque densities. Neurofibrillary tangles were often observed in the CA1 field and the inferior temporal cortex of non-demented individuals and were present in most cases with Alzheimer's disease. Conversely, the involvement of the superior frontal and occipital cortex was moderate even in demented patients. The distribution of senile plaques was homogeneous in all of the neocortical areas independently of the clinical diagnosis. Moreover, there was no correlation between the presence of heurofibrillary tangles and senile plaques in the cerebral regions studied. These results indicate a differential topography of neurofibrillary tangles and senile plaques, and suggest that overt clinical signs of Alzheimer's disease are linked to the progression of the neurodegenerative process in neocortical areas.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00294172
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  • 6
    Digitale Medien
    Digitale Medien
    Alzheimer's disease with asymmetric atrophy of the cerebral hemispheres: morphometric analysis of four cases (1994)
    Springer
    Acta neuropathologica 88 (1994), S. 440-447 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Senile plaques ; Neurofibrillary tangles ; Dementia ; Cortical atrophy ; Hemispheric specialization
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract To examine the clinicopathological correlations in rare Alzheimer's disease patients with asymmetric cerebral atrophy and to compare their pattern of cortical involvement by senile lesions with that observed in other cases with atypical Alzheimer's disease, we performed an extensive neuropathological analysis of the cerebral cortex in four such cases. Three patients presented with severe language impairment but relatively good preservation of praxis and gnosis even after several years of clinical evolution. Cerebral autopsies of these cases revealed a predominant left hemisphere atrophy. Conversely, in one case with marked right hemisphere atrophy, all of the cognitive functions were involved early in the course of dementia. Neurofibrillary tangles and senile plaques were preferentially localized in the prefrontal, temporal and posterior parietal cortex in both hemispheres, whereas the hippocampal formation displayed lower lesion densities than neocortical areas. Significantly higher neurofibrillary tangle and senile plaque densities were found in the more atrophic side in most of the areas studied. The ratio of neurofibrillary tangle and senile plaque densities between the two hemispheres was not correlated with the number of these lesions in the cerebral cortex. These results indicate that the degenerative process in demented cases with interhemispheric asymmetric cerebral atrophy is characterized by a widespread involvement of the neocortex by senile lesions and lacks clear regional topography of neurofibrillary tangle and senile plaque distribution. Moreover, the relative sparing of the hippocampus, comparable to that found in cases with focal progressive dementia, suggests that the dementing process may involve different cortical structures in cases with asymmetric cerebral atrophy than in typical Alzheimer's disease cases.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00389496
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  • 7
    Digitale Medien
    Digitale Medien
    Possible neuroprotective role of clusterin in Alzheimer’s disease: a quantitative immunocytochemical study (1998)
    Springer
    Acta neuropathologica 95 (1998), S. 387-394 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Alzheimer’s disease ; Cerebral cortex ; Clusterin ; Neurofibrillary tangle ; Neuronal loss
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Clusterin is a secreted glycoprotein that is expressed in response to tissue injury both in peripheral organs and in the brain. Recent studies have shown a substantial increase in clusterin mRNA in pyramidal neurons of the hippocampus and the entorhinal cortex in Alzheimer’s disease (AD), with clusterin immunoreactivity occurring in neuropil threads, neurofibrillary tangles (NFT), and senile plaques. To elucidate further the role of this protein in the degenerative process, a quantitative study of its distribution in the cerebral cortex of non-demented and AD patients, all older than 85 years of age, was performed using immunocytochemistry. Using a stereological approach, we found that in cortical areas affected in AD, such as the entorhinal, inferior temporal and superior frontal cortices, the percentage of NFT-free neurons displaying clusterin immunoreactivity was significantly higher than that in non-demented cases. No such increase in the density of clusterin-immunoreactive neurons was seen in cortical areas that were less affected in the disease process. Furthermore, clusterin immunoreactivity was rarely observed in NFT-containing neurons. In conjunction with previous observations in peripheral tissues, these data suggest that clusterin may have a neuroprotective role, and that in AD, low cellular expression of this protein may be associated with neuronal degeneration and death.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010050815
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  • 8
    Digitale Medien
    Digitale Medien
    Neuropathological changes in the cerebral cortex of 1258 cases from a geriatric hospital: retrospective clinicopathological evaluation of a 10-year autopsy population (1994)
    Springer
    Acta neuropathologica 87 (1994), S. 456-468 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words: Senile plaques – Neurofibrillary tangles – Dementia – Neocortex – Clinicopathological correlations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract. To examine the neuropathological and clinical characteristics of cerebral aging, we evaluated retrospectively a non-selected autopsy population of 1258 patients from the Geriatric Hospital of the University of Geneva School of Medecine. The prevalence of Alzheimer's disease increased with age below 90 years of age. In the nonagenarians and centenarians, there was a decline in the number of affected cases. The distribution with age of neurofibrillary tangles and senile plaques varied among the cortical areas studied. The CA1 field of the hippocampus and the inferior temporal cortex displayed increasing densities of neurofibrillary tangles with age, whereas the superior frontal and the occipital cortex were relatively spared, especially in patients in their tenth and eleventh decade. The percentage of cases presenting with senile plaques in the neocortex and hippocampal structure increased with age with a marked predominance of cases with moderate to high senile plaque densities. Neurofibrillary tangles were often observed in the CA1 field and the inferior temporal cortex of non-demented individuals and were present in most cases with Alzheimer's disease. Conversely, the involvement of the superior frontal and occipital cortex was moderate even in demented patients. The distribution of senile plaques was homogeneous in all of the neocortical areas independently of the clinical diagnosis. Moreover, there was no correlation between the presence of neurofibrillary tangles and senile plaques in the cerebral regions studied. These results indicate a differential topography of neurofibrillary tangles and senile plaques, and suggest that overt clinical signs of Alzheimer's disease are linked to the progression of the neurodegenerative process in neocortical areas.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00294172
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  • 9
    Digitale Medien
    Digitale Medien
    Quantitative immunohistochemical analysis of the distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of nonagenarians and centenarians (1993)
    Springer
    Acta neuropathologica 85 (1993), S. 602-610 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Senile plaques ; Neurofibrillary tangles ; Centenarians ; Immunohistochemistry ; Quantitative neuropathology
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary To investigate the neuropathological differences between normal aging and senile dementia of the Alzheimer type (SDAT) in very old people and to see how they compare with a younger population of demented elderly people, we performed an immunohistochemical quantitative analysis of the topography of senile plaques and neurofibrillary tangles in a series of 31 elderly patients aged from 96 to 102 years. According to the medical records, two groups were considered: 7 patients presenting with clinically documented SDAT and 24 patients with no or very mild cognitive impairment. The densities of senile plaques were comparable in both groups. Extensive neurofibrillary tangle formation was restricted to the CA1 hippocampal field of demented subjects, whereas the superior frontal cortex showed rare neurofibrillary tangles, independently of the clinical diagnosis. These results indicate an absence of direct correlation between the number of senile plaques and the clinical manifestation of SDAT. Furthermore, they suggest that the dementing process may involve different cortical structures in nonagenarians and centenarians than in younger demented individuals where a widespread cortical involvement is generally observed. Thus, the neurofibrillary tangle density in the CA1 field may be critical for the neuropathological diagnosis of SDAT in this particular group of very old patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00334669
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  • 10
    Digitale Medien
    Digitale Medien
    A laser microprobe mass analysis of trace elements in brain mineralizations and capillaries in Fahr’s disease (1996)
    Springer
    Acta neuropathologica 92 (1996), S. 351-357 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Key words Aluminum ; Fahr’s disease ; Laser ; microprobe mass analysis ; Mineralizations ; Trace ; elements
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We report a detailed analysis of the content of aluminum, iron, zinc, copper, calcium, and magnesium in the non-vascular and pericapillary mineralizations and the normal capillaries of the globus pallidus and dentate nucleus of the cerebellum in two patients with clinically and neuropathologically confirmed Fahr’s disease. The study employed laser microprobe mass analysis, a technique that enables highly sensitive detection of the levels of trace elements. In the globus pallidus, there was a significant increase in aluminum-, iron-, zinc-, and calcium-related peak intensity in the pericapillary and non-vascular mineralizations compared to the normal capillaries. The pericapillary and non-vascular mineralizations had comparable concentrations of these elements. No difference was found in copper levels between the different probe sites. Magnesium was almost absent in pericapillary mineralizations and normal capillaries, while it accumulated within non-vascular mineralizations. In the cerebellar dentate nucleus, non-vascular mineralizations displayed higher concentrations of all of these elements than normal capillaries, while pericapillary mineralizations had a higher aluminum and lower iron, copper, and calcium content than did non-vascular mineralizations. Zinc and magnesium were selectively deposited within the non-vascular mineralizations in this nucleus. Furthermore, the element composition of non-vascular mineralizations differed between the globus pallidus and dentate nucleus. These findings indicate that the formation of pericapillary and non-vascular mineralizations may be two independent phenomena which coexist in the course of Fahr’s disease. The marked qualitative and quantitative differences in trace element content in non-vascular mineralizations between the globus pallidus and cerebellar dentate nucleus suggest that the involvement of trace elements in the pathogenesis of Fahr’s disease is probably indirect.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004010050529
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