Alzheimer's disease-like alterations in peripheral cells from presenilin-1transgenic mice

Many cases of early-onset inherited Alzheimer's disease (AD) are caused by mutations in the presenilin-1 (PS1) gene. Expression of PS1 mutations in ce ll culture systems and in primary neurons from transgenic mice increases th eir vulnerability to cell death. Interestingly, enhanced vulnerability to c ell death has also been demonstrated for peripheral lymphocytes from AD pat ients. We now report that lymphocytes from PS1 mutant transgenic mice show a similar hypersensitivity to cell death as do peripheral cells from AD pat ients and several cell culture systems expressing PS1 mutations. The cell d eath-enhancing action of mutant PS1 was associated with increased productio n of reactive oxygen species and altered calcium regulation, but not with c hanges of mitochondrial cytochrome c. Our study further emphasizes the path ogenic role of mutant PS1 and may provide the fundamental basis for new eff orts to close the gap between studies using neuronal cell lines transfected with mutant PS1, neurons from transgenic animals, and peripheral cells fro m AD patients. (C) 2001 Academic Press.