title: Lifespan profiles of Alzheimer's disease-associated genes and products in monkeys and mice.
abstract: Alzheimer's disease (AD) is characterized by plaques of amyloid-beta (Abeta) peptide, cleaved from amyloid-beta protein precursor (AbetaPP). Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AbetaPP mRNA, AbetaPP protein, and Abeta levels in rodents and primates. We also tracked a transcriptional regulator of the AbetaPP gene, specificity protein 1 (SP1), and the beta amyloid precursor cleaving enzyme (BACE1). In mice, AbetaPP and SP1 mRNA and their protein products were elevated late in life; Abeta levels declined in old age. In monkeys, SP1, AbetaPP, and BACE1 mRNA declined in old age, while protein products and Abeta levels rose. Proteolytic processing in both species did not match production of Abeta. In primates, AbetaPP and SP1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products as well as Abeta levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age-related diseases.
authors: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA.
authors: Remi
authors: R
authors: Dosunmu
authors: Jinfang
authors: J
authors: Wu
authors: Lina
authors: L
authors: Adwan
authors: Bryan
authors: B
authors: Maloney
authors: Md Riyaz
authors: MR
authors: Basha
authors: Christopher A
authors: CA
authors: McPherson
authors: G Jean
authors: GJ
authors: Harry
authors: Deborah C
authors: DC
authors: Rice
authors: Nasser H
authors: NH
authors: Zawia
authors: Debomoy K
authors: DK
authors: Lahiri
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics*; D000818:Animals; D000882:Haplorhini; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics
chemical_list: D014157:Transcription Factors