Fas and activated caspase 8 in normal, Alzheimer and multiple infarct brains.
Using immunohistochemistry, Fas and caspase 8 positive sites were localized in the brains of Alzheimer patients and those with multiple infarcts as well as age-matched normal. The frontal, occipital and hippocampal regions were dissected out from these patients and normal individuals shortly after death. Positive Fas neurons were found in all these regions of normal individuals and Alzheimer patients, but not in the brains of patients with multiple infarct. Activated caspase 8 protein was found only in the brains of Alzheimer patients and not in the other groups. Plaques in the Alzheimer patients were positive for Fas and activated caspase 8. The former was localized in the membrane and the inside of the plaque whereas activated caspase 8 was only present in the interior of the plaque, as revealed by confocal microscopy. Our study shows that caspase 8 was activated in the Alzheimer brain and the presence of Fas and activated caspase 8 points to a possibility that at least some plaques were of intracellular origin as Fas was a cell membrane receptor and caspase 8 was a intracellular enzyme downstream to Fas. Furthermore, we had confirmed that in most neurons Fas and caspase 8 did not exist concomitantly and that the glial cells (astrocytes) did not express caspase 8 in Alzheimer patients.
Department of Anatomy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR, China. david-yew@cuhk.edu.hk
David T
DT
Yew
Wei
W
Ping Li
W K
WK
Liu
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D020520:Brain Infarction / Q000201:enzymology / Q000378:metabolism*; D016022:Case-Control Studies; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011180:Postmortem Changes; D019014:fas Receptor / Q000378:metabolism*
D005904:Glial Fibrillary Acidic Protein; D019014:fas Receptor; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases