title: In situ hybridization analysis of presenilin 1 mRNA in Alzheimer disease and in lesioned rat brain.
abstract: Presenilin-1 (PS-1) gene mutations are responsible for the majority of the early onset familial forms of Alzheimer disease (AD). Neither PS-1's anatomic distribution in brain nor expression in AD have been reported. Using in situ hybridization in the rat forebrain, we show that PS-1 mRNA expression is primarily in cortical and hippocampal neurons, with less expression in subcortical structures, in a regional pattern similar to APP695. Excitotoxic lesions lead to loss of PS-1 signal. A neuronal pattern of expression of PS-1 mRNA was also observed in the human hippocampal formation. AD and control levels did not differ. PS-1 is expressed in brain areas vulnerable to AD changes more so than in areas spared in AD; however, PS-1 expression is not sufficient to mark vulnerable regions. Collectively, these data suggest that the neuropathogenic process consequent to PS-1 mutations begins in neuronal cell populations.
authors.affiliation: Laboratory of Genetics and Aging, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
authors.forename: K
authors.initials: K
authors.lastname: Page
authors.forename: R
authors.initials: R
authors.lastname: Hollister
authors.forename: R E
authors.initials: RE
authors.lastname: Tanzi
authors.forename: B T
authors.initials: BT
authors.lastname: Hyman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D015415:Biomarkers; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D015345:Oligonucleotide Probes; D053764:Presenilin-1; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D014158:Transcription, Genetic
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; D015345:Oligonucleotide Probes; C508853:PSEN1 protein, human; D053764:Presenilin-1; D012333:RNA, Messenger