TY - JOUR
T1 - Lifespan profiles of Alzheimer's disease-associated genes and products in monkeys and mice
AU - Dosunmu, Remi
AU - Wu, Jinfang
AU - Adwan, Lina
AU - Maloney, Bryan
AU - Basha, Md Riyaz
AU - McPherson, Christopher A.
AU - Harry, G. Jean
AU - Rice, Deborah C.
AU - Zawia, Nasser H.
AU - Lahiri, Debomoy K.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Amyloid-β protein precursor (AβPP)
KW - Amyloidogenesis
KW - BACE1
KW - Development
KW - Primates
KW - Rodents
KW - Specificity protein 1 (SP1)
KW - Transcription
UR - http://www.scopus.com/inward/record.url?scp=70349140909&partnerID=8YFLogxK
U2 - 10.3233/JAD-2009-1138
DO - 10.3233/JAD-2009-1138
M3 - Review article
C2 - 19584442
AN - SCOPUS:70349140909
SN - 1387-2877
VL - 18
SP - 211
EP - 230
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 1
ER -