cqvip: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.
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