Differential distribution of presenilin-1, Bax, and Bcl-X-L in Alzheimer'sdisease and frontotemporal dementia

We have previously reported that presenilin-1 (PS-1)-immunoreactive neurons survive in late-onset sporadic Alzheimer's disease (AD). To examine if thi s is also the case in other dementing conditions, and if it is associated w ith changes in the expression of the main apoptosis-related proteins, a qua ntitative immunocytochemical study of presenilin-1, Bar, and Bcl-X-L in the cerebral cortex of non-demented and AD patients, and patients with frontot emporal dementia (FTD) was performed. In nondemented cases, the frequency o f neurons showing PS-1 immunoreactivity was 25-60%, Bar immunoreactivity 36 -54%, and Bcl-X-L immunoreactivity 26-63% depending on the cortical area. T he frequency of NFT-free neurons which contained PS-1 or Bar was consistent ly increased in all of the areas in AD. In FTD cases, the percentage of PS- 1-, but not Bax-immunoreactive neurons was increased only in areas displayi ng a substantial neuronal loss. Conversely, there was no difference in the densities of Bcl-X-L-containing neurons among the three diagnosis groups. T hese data suggest that surviving neurons in affected cortical areas in AD s how a high expression of PS-1 and Bar, indicating that these proteins play a key role in the mechanisms of cell death in this disorder. In FTD, neuron s containing PS-1 are preserved, further supporting a neuroprotective role for this protein in other neurodegenerative disorders.