Alterations in beta-amyloid production and deposition in brain regions of two transgenic models.
Mutations in the amyloid precursor protein (APP) gene are associated with altered production and deposition of amyloid beta (Abeta) peptide in the Alzheimer's disease (AD) brain. The pathways that regulate APP processing, Abeta production and Abeta deposition in different tissues and brain regions remain unclear. To address this, we examined levels of various APP processing products as well as Abeta deposition in a genomic-based (R1.40) and a cDNA-based (Tg2576) transgenic mouse model of AD. In tissues, only brain generated detectable levels of the penultimate precursor to Abeta, APP C-terminal fragment-beta. In brain regions, holoAPP levels remained constant, but ratios of APP C-terminal fragments and levels of Abeta differed significantly. Surprisingly, cortex had the lowest steady-state levels of Abeta compared to other brain regions. Comparison of Abeta deposition in Tg2576 and R1.40 animals revealed that R1.40 exhibited more abundant deposition in cortex while Tg2576 exhibited extensive deposition in the hippocampus. Our results suggest that AD transgenic models are not equal; their unique characteristics must be considered when studying AD pathogenesis and therapies.
Lehman
Emily J H
EJ
Department of Genetics and Neurosciences, Center for Human Genetics, Case Western Reserve University, University Center for Memory and Aging and Ireland Cancer Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA.
Kulnane
Laura Shapiro
LS
Lamb
Bruce T
BT
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004423:Ear / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005123:Eye / Q000378:metabolism / Q000473:pathology; D005260:Female; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009830:Olfactory Bulb / Q000378:metabolism / Q000473:pathology; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D013045:Species Specificity; D013737:Testis / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)