gamma-Secretase is a key enzyme involved in the processing of the beta-amyloid 
precursor protein into amyloid beta-peptides (Abeta). Abeta accumulates and 
forms plaques in Alzheimer's disease (AD) brains. A progressive 
neurodegeneration and cognitive decline occurs during the course of the disease, 
and Abeta is believed to be central for the molecular pathogenesis of AD. 
Apoptosis has been implicated as one of the mechanisms behind the neuronal cell 
loss seen in AD. We have studied preservation and activity of the 
gamma-secretase complex during apoptosis in neuroblastoma cells (SH-SY5Y) 
exposed to staurosporine (STS). We report that the known components (presenilin, 
Nicastrin, Aph-1 and Pen-2) interact and form active gamma-secretase complexes 
in apoptotic cells. In addition, the fragments corresponding to the PS1 
N-terminal fragment and the caspase-cleaved PS1 C-terminal fragment 
(PS1-caspCTF) were found to form active gamma-secretase complexes when 
co-expressed in presenilin (PS) knockout cells. Interestingly, PS1-caspCTF 
replaced the normal PS1 C-terminal fragment and was co-immunoprecipitated with 
the gamma-secretase complex in SH-SY5Y cells exposed to STS. In addition, Abeta 
was detected in medium from apoptotic HEK APP(swe) cells. Together, the data 
show that gamma-secretase complexes containing PS1-caspCTF are active, and 
suggest that this proteolytic activity is also important in dying cells and may 
affect the progression of AD.