Fas and Fas ligand expression in Alzheimer's disease

The Fas/Fas ligand (L) signaling system has been implicated in the control of cell death and cell survival of T and B lymphocytes and in a variety of cell types under particular pathological conditions. In the present study w e examined the expression of Fas and Fas-L, by Western blotting and immunoh istochemistry, in the human frontal cortex and hippocampus of individuals w ith advanced Alzheimer's disease (AD) and age-matched controls. Expression levels of Fas and Fas-L, as seen in Western blots, are preserved in the fro ntal cortex but decreased in the hippocampus in AD when compared with age-m atched controls. Yet Fas and Fas-L immunoreactivity is found in remaining A D neurons in the frontal cortex and hippocampus. Moreover, Fas and Fas-L ar e expressed equally in tangle-bearing and non-tangle-bearing neurons, as re vealed with double-labeling immunohistochemistry to Fas or Fas-L and tau or phosphorylated neurofilament epitopes. Dystrophic neurites of senile plaqu es are not stained with Fas and Fas-L antibodies. A moderate increase in Fa s and a strong increase in Fas-L immunoreactivity occur in reactive astrocy tes in AD. Yet there is no relationship between Fas or Fas-L expression and increased nuclear DNA vulnerability as revealed with double-labeling immun ohistochemistry and in situ end-labeling of nuclear DNA fragmentation. Alth ough the Fas/Fas-L system may have some effect in the control of reactive a strocytosis in AD, the present results show no evidence that Fas/Fas-L sign als participate in specific processes of the disease, including neurofibril lary degeneration, dystrophic neurite formation, and cell death.