DNA damage and activated caspase-3 expression in neurons and astrocytes: evidence for apoptosis in frontotemporal dementia

Exp Neurol. 2000 May;163(1):9-19. doi: 10.1006/exnr.2000.7340.


Frontotemporal dementia (FTD) is a neurodegenerative disease which affects mainly the frontal and anterior temporal cortex. It is associated with neuronal loss, gliosis, and microvacuolation of lamina I to III in these brain regions. In previous studies we have described neurons with DNA damage in the absence of tangle formation and suggested this may result in tangle-independent mechanisms of neurodegeneration in the AD brain. In the present study, we sought to examine DNA fragmentation and activated caspase-3 expression in FTD brain where tangle formation is largely absent. The results demonstrate that numerous nuclei were TdT positive in all FTD brains examined. Activated caspase-3 immunoreactivity was detected in both neurons and astrocytes and was elevated in FTD cases as compared to control cases. A subset of activated caspase-3-positive cells were also TdT positive. In addition, the cell bodies of a subset of astrocytes showed enlarged, irregular shapes, and vacuolation and their processes appeared fragmented. These degenerating astrocytes were positive for activated caspase-3 and colocalized with robust TdT-labeled nuclei. These findings suggest that a subset of astrocytes exhibit degeneration and that DNA damage and activated caspase-3 may contribute to neuronal cell death and astrocyte degeneration in the FTD brain. Our results suggest that apoptosis may be a mechanism of neuronal cell death in FTD as well as in AD (228).

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Astrocytes / enzymology*
  • Astrocytes / pathology
  • Behavioral Symptoms / diagnosis
  • Brain / enzymology
  • Brain / pathology
  • Caspase 3
  • Caspases / metabolism*
  • Cell Nucleus / enzymology
  • Cell Nucleus / pathology
  • DNA Damage*
  • DNA Fragmentation
  • Dementia / diagnosis
  • Dementia / pathology*
  • Dementia / physiopathology*
  • Fatal Outcome
  • Female
  • Frontal Lobe / enzymology
  • Frontal Lobe / pathology
  • Glial Fibrillary Acidic Protein / metabolism
  • Gliosis
  • Humans
  • Male
  • Middle Aged
  • Neurites / enzymology
  • Neurites / pathology
  • Neurons / enzymology*
  • Neurons / pathology
  • Pyramidal Cells / enzymology
  • Pyramidal Cells / pathology
  • Temporal Lobe / enzymology
  • Temporal Lobe / pathology


  • Glial Fibrillary Acidic Protein
  • CASP3 protein, human
  • Caspase 3
  • Caspases