The main unifying feature of cases with frontotemporal dementia (FTD) is the p attern of brain atrophy. Surprisingly, there are a variety of underlying histopa thologies in cases with the clinical features and typical...The main unifying feature of cases with frontotemporal dementia (FTD) is the p attern of brain atrophy. Surprisingly, there are a variety of underlying histopa thologies in cases with the clinical features and typical pattern of atrophy cha racterizing FTD. This suggests that the degenerative mechanism(s) associated wit h pyramidal cell loss and gliosis in FTD is likely to be similar in the differen t histopathological forms of the disease. In this study we tested this hypothesi s by analysing a common cell death mechanism, apoptosis, in cases of FTD with ei ther Picks disease (PiD) (n = 9) or frontotemporal lobar degeneration (FTLD) ( n = 7) compared with normal controls (n = 10). Tissue sections from previously a nalysed cases were stained using anti activated caspase-3 immunohistochemistry , TUNEL, propidium iodide, and cell and pathology specific labels. These marke rs of apoptosis identified both astrocytes and neurons in regions vulnerable to degeneration in all cases of FTD. However, neuronal apoptosis was rare (<2 %of neurons), even at early disease stages where there is considerably less fro ntotemporal atrophy or pyramidal cell loss. This suggests that other cell death mechanisms account for the progressive neuronal loss in FTD. In contrast, astroc ytes with beaded processes and other apoptotic features were very frequent in bo th PiD and FTLD, with the severity of astrocytosis and astrocytic apoptosis corr elating with both the degree of neuronal loss and the stage of disease. These fi ndings provide evidence that astrocytic apoptosis occurs as an early event in di fferent histopathological forms of FTD. Furthermore, this astrocytic apoptosis d irectly relates to the degree of degeneration in FTD, and becomes the overwhelmi ng pathological feature as the disease progresses.展开更多
Objectives: To determine if apolipoprotein E 4 influences the frequency of Alz heimer type pathologic features in tauopathies, synucleinopathies, and frontote mporal degeneration and to determine if the frequency of A...Objectives: To determine if apolipoprotein E 4 influences the frequency of Alz heimer type pathologic features in tauopathies, synucleinopathies, and frontote mporal degeneration and to determine if the frequency of Alzheimer type patholo gic features in synucleinopathies is similar to the frequency of such features i n tauopathies and frontotemporal degeneration. Methods: A total of 285 patients with pathologically proven neurodegenerative disorders, including diffuse and tr ansitional Lewy body disease, frontotemporal degeneration, progressive supranucl ear palsy, corticobasal degeneration, and multiple system atrophy, with a mean a ge of 75.1 ±.9.3 years, were suitable for genetic and pathological analysis. Di sorders were grouped as tauopathies (progressive supranuclear palsy and corticob asal degeneration), synucleinopathies (Lewy body disease and multiple system atr ophy), and frontotemporal degeneration. Braak neurofibrillary tangle staging and quantitative scores of senile plaques were used to determine the degree of conc omitant Alzheimer type pathologic features in each case, and apolipoprotein E g enotype was determined from DNA isolated from frozen brain tissue. The relations hip of apolipoprotein E 4 to Alzheimer type pathologic features was determined. Results: Across all neurodegenerative disorders, apolipoprotein E 4 and older a ge independently predicted the co occurrence of Alzheimer type pathologic feat ures (P<.001), whereas female sex had a lesser effect (P = .03). When divided in to the 3 subgroups (tauopathies, synucleinopathies, and frontotemporal degenerat ion), apolipoproteinE 4 had a similar effect, whereas older age and female sex w ere less predictive. There was a significant difference between the frequency of Alzheimer type pathologic features in synucleinopathies and the frequency of s uch features in tauopathies and frontotemporal degeneration (P<.001 for both). T he frequency of apolipoprotein E 4 allele was not significantly different among the 3 groups. Conclusions: Apolipoprotein E 4, independent of older age and sex, contributes to the co occurrence of Alzheimer type pathologic features in tau opathies, synucleinopathies, and frontotemporal degeneration, but this does not explain why Alzheimer type pathologic features are significantly more likely to coexist with synucleinopathies than with either tauopathies or frontotemporal d egeneration.展开更多
文摘The main unifying feature of cases with frontotemporal dementia (FTD) is the p attern of brain atrophy. Surprisingly, there are a variety of underlying histopa thologies in cases with the clinical features and typical pattern of atrophy cha racterizing FTD. This suggests that the degenerative mechanism(s) associated wit h pyramidal cell loss and gliosis in FTD is likely to be similar in the differen t histopathological forms of the disease. In this study we tested this hypothesi s by analysing a common cell death mechanism, apoptosis, in cases of FTD with ei ther Picks disease (PiD) (n = 9) or frontotemporal lobar degeneration (FTLD) ( n = 7) compared with normal controls (n = 10). Tissue sections from previously a nalysed cases were stained using anti activated caspase-3 immunohistochemistry , TUNEL, propidium iodide, and cell and pathology specific labels. These marke rs of apoptosis identified both astrocytes and neurons in regions vulnerable to degeneration in all cases of FTD. However, neuronal apoptosis was rare (<2 %of neurons), even at early disease stages where there is considerably less fro ntotemporal atrophy or pyramidal cell loss. This suggests that other cell death mechanisms account for the progressive neuronal loss in FTD. In contrast, astroc ytes with beaded processes and other apoptotic features were very frequent in bo th PiD and FTLD, with the severity of astrocytosis and astrocytic apoptosis corr elating with both the degree of neuronal loss and the stage of disease. These fi ndings provide evidence that astrocytic apoptosis occurs as an early event in di fferent histopathological forms of FTD. Furthermore, this astrocytic apoptosis d irectly relates to the degree of degeneration in FTD, and becomes the overwhelmi ng pathological feature as the disease progresses.
文摘Objectives: To determine if apolipoprotein E 4 influences the frequency of Alz heimer type pathologic features in tauopathies, synucleinopathies, and frontote mporal degeneration and to determine if the frequency of Alzheimer type patholo gic features in synucleinopathies is similar to the frequency of such features i n tauopathies and frontotemporal degeneration. Methods: A total of 285 patients with pathologically proven neurodegenerative disorders, including diffuse and tr ansitional Lewy body disease, frontotemporal degeneration, progressive supranucl ear palsy, corticobasal degeneration, and multiple system atrophy, with a mean a ge of 75.1 ±.9.3 years, were suitable for genetic and pathological analysis. Di sorders were grouped as tauopathies (progressive supranuclear palsy and corticob asal degeneration), synucleinopathies (Lewy body disease and multiple system atr ophy), and frontotemporal degeneration. Braak neurofibrillary tangle staging and quantitative scores of senile plaques were used to determine the degree of conc omitant Alzheimer type pathologic features in each case, and apolipoprotein E g enotype was determined from DNA isolated from frozen brain tissue. The relations hip of apolipoprotein E 4 to Alzheimer type pathologic features was determined. Results: Across all neurodegenerative disorders, apolipoprotein E 4 and older a ge independently predicted the co occurrence of Alzheimer type pathologic feat ures (P<.001), whereas female sex had a lesser effect (P = .03). When divided in to the 3 subgroups (tauopathies, synucleinopathies, and frontotemporal degenerat ion), apolipoproteinE 4 had a similar effect, whereas older age and female sex w ere less predictive. There was a significant difference between the frequency of Alzheimer type pathologic features in synucleinopathies and the frequency of s uch features in tauopathies and frontotemporal degeneration (P<.001 for both). T he frequency of apolipoprotein E 4 allele was not significantly different among the 3 groups. Conclusions: Apolipoprotein E 4, independent of older age and sex, contributes to the co occurrence of Alzheimer type pathologic features in tau opathies, synucleinopathies, and frontotemporal degeneration, but this does not explain why Alzheimer type pathologic features are significantly more likely to coexist with synucleinopathies than with either tauopathies or frontotemporal d egeneration.
