title: Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells.
abstract: Mutations in two recently identified genes appear to cause the majority of early-onset familial Alzheimer's disease (FAD). These two novel genes, presenilin 1 (PS1) and presenilin 2 (PS2) are members of an evolutionarily conserved gene family. The normal biological role(s) of the presenilins and the mechanism(s) by which the FAD-associated mutations exert their effect remain unknown. Employing in situ hybridization, we demonstrate that the expression patterns of PS1 and PS2 in the brain are extremely similar to each other and that messages for both are primarily detectable in neuronal populations. Immunochemical analyses indicate 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 either their migration patterns on SDS-polyacrylamide gel electrophoresis or their overall subcellular localization, although subtle differences in perinuclear staining were noted for mutant PS1.
authors.affiliation: Genetics and Aging Unit, Massachusetts General Hospital-East, Harvard Medical School, Charlestown 02129, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Kovacs
authors.forename: H J
authors.initials: HJ
authors.lastname: Fausett
authors.forename: K J
authors.initials: KJ
authors.lastname: Page
authors.forename: T W
authors.initials: TW
authors.lastname: Kim
authors.forename: R D
authors.initials: RD
authors.lastname: Moir
authors.forename: D E
authors.initials: DE
authors.lastname: Merriam
authors.forename: R D
authors.initials: RD
authors.lastname: Hollister
authors.forename: O G
authors.initials: OG
authors.lastname: Hallmark
authors.forename: R
authors.initials: R
authors.lastname: Mancini
authors.forename: K M
authors.initials: KM
authors.lastname: Felsenstein
authors.forename: B T
authors.initials: BT
authors.lastname: Hyman
authors.forename: R E
authors.initials: RE
authors.lastname: Tanzi
authors.forename: W
authors.initials: W
authors.lastname: Wasco
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D015415:Biomarkers; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1; D053766:Presenilin-2 / Q000032:analysis* / Q000235:genetics; D015347:RNA Probes; D051381:Rats
chemical_list: D015415:Biomarkers; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; C000607793:Psen1 protein, rat; C000607794:Psen2 protein, rat; D015347:RNA Probes