Presenilins in memory, Alzheimer's disease, and therapy

Presenilins are considered to be the catalytic subunits of the gamma-secretase complex and are therefore drug targets for Alzheimer's disease. They are also essential for the fine tuning of the immunological system and for memory and synaptic plasticity. Genetic ablation in the forebrain results in a progressive neurodegenerative process that is independent from Abeta generation. The question arises as to what extent these observations should influence our thinking on the pathogenesis of Alzheimer's disease and on strategies to further develop gamma-secretase inhibitors.