ALZHEIMER-ASSOCIATED PRESENILIN-1 AND PRESENILIN-2 - NEURONAL EXPRESSION IN BRAIN AND LOCALIZATION TO INTRACELLULAR MEMBRANES IN MAMMALIAN-CELLS

Mutations in two recently identified genes appear to cause the majorit y of early-onset familial Alzheimer's disease (FAD). These two novel g enes, presenilin 1 (PS1) and presenilin 2 (PS2) are members of an evol utionarily conserved gene family. The normal biological role(s) of the presenilins and the mechanism(s) by which the FAD-associated mutation s exert their effect remain unknown. Employing in situ hybridization, we demonstrate that the expression patterns of PS1 and PS2 in the brai n are extremely similar to each other and that messages for both are p rimarily detectable in neuronal populations. Immunochemical analyses i ndicate that PS1 and PS2 are similar in size and localized to similar intracellular compartments (endoplasmic reticulum and Golgi complex). FAD-associated mutations in PS1 and PS2 do not significantly modify ei ther their migration patterns on SDS-polyacrylamide gel electrophoresi s or their overall subcellular localization, although subtle differenc es in perinuclear staining were noted for mutant PS1.