Lifespan profiles of Alzheimer's disease-associated genes and products in monkeys and mice

Remi Dosunmu, Jinfang Wu, Lina Adwan, Bryan Maloney, Md Riyaz Basha, Christopher A. McPherson, G. Jean Harry, Deborah C. Rice, Nasser H. Zawia, Debomoy Lahiri

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is characterized by plaques of amyloid-β (Aβ) peptide, cleaved from amyloid-β protein precursor (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.

Original languageEnglish
Pages (from-to)211-230
Number of pages20
JournalJournal of Alzheimer's Disease
Volume18
Issue number1
DOIs
StatePublished - 2009

Fingerprint

Amyloid beta-Protein Precursor
Haplorhini
Alzheimer Disease
Messenger RNA
Genes
Proteins
Primates
Enzyme Precursors
Amyloid Plaques
Staphylococcal Protein A
Amyloid
Rodentia
Peptides

Keywords

  • Amyloid-β protein precursor (AβPP)
  • Amyloidogenesis
  • BACE1
  • Development
  • Primates
  • Rodents
  • Specificity protein 1 (SP1)
  • Transcription

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

Cite this

Lifespan profiles of Alzheimer's disease-associated genes and products in monkeys and mice. / Dosunmu, Remi; Wu, Jinfang; Adwan, Lina; Maloney, Bryan; Basha, Md Riyaz; McPherson, Christopher A.; Harry, G. Jean; Rice, Deborah C.; Zawia, Nasser H.; Lahiri, Debomoy.

In: Journal of Alzheimer's Disease, Vol. 18, No. 1, 2009, p. 211-230.

Research output: Contribution to journalArticle

Dosunmu, R, Wu, J, Adwan, L, Maloney, B, Basha, MR, McPherson, CA, Harry, GJ, Rice, DC, Zawia, NH & Lahiri, D 2009, 'Lifespan profiles of Alzheimer's disease-associated genes and products in monkeys and mice', Journal of Alzheimer's Disease, vol. 18, no. 1, pp. 211-230. https://doi.org/10.3233/JAD-2009-1138
Dosunmu, Remi ; Wu, Jinfang ; Adwan, Lina ; Maloney, Bryan ; Basha, Md Riyaz ; McPherson, Christopher A. ; Harry, G. Jean ; Rice, Deborah C. ; Zawia, Nasser H. ; Lahiri, Debomoy. / Lifespan profiles of Alzheimer's disease-associated genes and products in monkeys and mice. In: Journal of Alzheimer's Disease. 2009 ; Vol. 18, No. 1. pp. 211-230.
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