Mice expressing human mutant presenilin-1 exhibit decreased activation of NF-kappaB p50 in hippocampal neurons after injury.

Mutations in the presenilin-1 (mutPS-1) gene, a cause of familial Alzheimer's disease, increase the susceptibility of neurons to apoptotic death. Using the trimethyltin model of hippocampal neurodegeneration, mice expressing the human mutPS-1 gene (M146L) exhibited increased neurodegeneration and mortality relative to non-transgenic littermates. Activation of NF-kappaB p50 was found to be impaired in transgenic mice with unaltered expression levels suggesting that mutPS-1 expression inhibits p50 activation to adversely affect neuronal resistance to injury.