Alterations in β-amyloid production and deposition in brain regions of two transgenic models

• Published in: Neurobiology of aging 2003-09, Vol.24 (5), p.645-653
• Main Authors: Lehman, Emily J.H, Kulnane, Laura Shapiro, Lamb, Bruce T
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer’s disease; Amyloid beta-Peptides - genetics; Amyloid beta-Peptides - metabolism; Amyloid precursor protein; Amyloid-β; Animals; Biological and medical sciences; Blotting, Western; Brain - metabolism; Brain - pathology; cDNA-based; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Ear - pathology; Enzyme-Linked Immunosorbent Assay; Eye - metabolism; Eye - pathology; Female; Genomic-based; Kidney - metabolism; Kidney - pathology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Neurology; Olfactory Bulb - metabolism; Olfactory Bulb - pathology; Pancreas - metabolism; Pancreas - pathology; Peptide Fragments - metabolism; Species Specificity; Testis - metabolism; Testis - pathology; Tissue Distribution; Transgenic mice
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/S0197-4580(02)00153-7

Mutations in the amyloid precursor protein (APP) gene are associated with altered production and deposition of amyloid beta (Aβ) peptide in the Alzheimer’s disease (AD) brain. The pathways that regulate APP processing, Aβ production and Aβ deposition in different tissues and brain regions remain unclear. To address this, we examined levels of various APP processing products as well as Aβ 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 Aβ, APP C-terminal fragment-β. In brain regions, holoAPP levels remained constant, but ratios of APP C-terminal fragments and levels of Aβ differed significantly. Surprisingly, cortex had the lowest steady-state levels of Aβ compared to other brain regions. Comparison of Aβ 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.