Presenilin is required for proper morphology and function of neurons in C-elegans

Mutations in the human presenilin genes cause the most frequent and aggress ive forms of familial Alzheimer's disease (FAD)(1). Here we show that in ad dition to its role in cell fate decisions in nonneuronal tissues(2-4), pres enilin activity is required in terminally differentiated neurons in vivo. M utations in the Caenorhabditis elegans presenilin genes sel-12 and hop-1 re sult in a defect in the temperature memory of the animals. This defect is c aused by the loss of presenilin function in two cholinergic interneurons th at display neurite morphology defects in presenilin mutants. The morphology and function of the affected neurons in sel-12 mutant animals can be resto red by expressing sel-12 only in these cells. The wild-type human presenili n PS1, but not the FAD mutant PS1 A246E, can also rescue these morphologica l defects. As lin-12 mutant animals display similar morphological and funct ional defects to presenilin mutants, we suggest that presenilins mediate th eir activity in postmitotic neurons by facilitating Notch signalling. These data indicate cell-autonomous and evolutionarily conserved control of neur al morphology and function by presenilins.