Lifespan profiles of Alzheimer's disease–associated genes and their products in monkeys and mice.

dc.contributor.authorDosunmu, Remi
dc.contributor.authorWu, Jinfang
dc.contributor.authorAdwan, Lina
dc.contributor.authorMaloney, Bryan
dc.contributor.authorBasha, Md Riyaz
dc.contributor.authorMcPherson, Christopher A.
dc.contributor.authorHarry, G. Jean
dc.contributor.authorRice, Deborah C.
dc.contributor.authorZawia, Nasser H.
dc.contributor.authorLahiri, Debomoy K.
dc.contributor.departmentDepartment of Psychiatry, IU School of Medicineen_US
dc.date.accessioned2016-03-30T23:19:39Z
dc.date.available2016-03-30T23:19:39Z
dc.date.issued2009
dc.description.abstractAlzheimer's disease (AD) is characterized by plaques of amyloid–beta (Aβ) peptide, cleaved from amyloid–β precursor protein (AβPP). 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 AβPP mRNA, AβPP protein, and Aβ levels in rodents and primates. We also tracked a transcriptional regulator of the AβPP gene, specificity protein 1 (SP1), and the β amyloid precursor cleaving enzyme (BACE1). In mice, AβPP and Sp1 mRNA and their protein products were elevated late in life; Aβ levels declined in old age. In monkeys, Sp1, AβPP, and BACE1 mRNA declined in old age, while protein products and Aβ levels rose. Proteolytic processing in both species did not match production of Aβ. In primates, AβPP and Sp1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products, as well as Aβ 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.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationDosunmu, R., Wu, J., Adwan, L., Maloney, B., Basha, M. R., McPherson, C. A., … Lahiri, D. K. (2009). Lifespan Profiles of Alzheimer’s Disease-Associated Genes and Products in Monkeys and Mice. Journal of Alzheimer’s Disease, 18(1), 211–230. http://doi.org/10.3233/JAD-2009-1138en_US
dc.identifier.issn1387-2877 1875-8908en_US
dc.identifier.urihttps://hdl.handle.net/1805/9099
dc.language.isoen_USen_US
dc.publisherIOSen_US
dc.relation.isversionof10.3233/JAD-2009-1138en_US
dc.relation.journalJournal of Alzheimer's disease : JADen_US
dc.rightsPublisher's policyen_US
dc.sourcePMCen_US
dc.subjectAmyloid-β protein precursor (AβPP)en_US
dc.subjectamyloidogenesisen_US
dc.subjectBACE1en_US
dc.subjectdevelopmenten_US
dc.subjectprimatesen_US
dc.subjectrodentsen_US
dc.subjectspecificity protein 1 (SP1)en_US
dc.subjecttranscriptionen_US
dc.titleLifespan profiles of Alzheimer's disease–associated genes and their products in monkeys and mice.en_US
dc.typeArticleen_US
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