Alterations in β-amyloid production and deposition in brain regions of two transgenic models
Abstract
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.
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The R1.40 model exhibits gradual deposition of primarily Aβ40.
“we mated Cx3cr1 knockout mice to two different mouse models of AD that exhibit either rapid deposition of primarily A42 (the APPPS1 model) 21 or gradual deposition of primarily A40 (the R1.40 model).[22][23][24]”
From CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models (2010) · cites this paper as [24]
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Self-citationNuclear localization of Cdk5 is a key determinant in the postmitotic state of neurons
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- Authors
- Lehman, E. J. H., Kulnane, L. S., & Lamb, B. T.
- Affiliations
- University Hospitals of Cleveland (US)
- Corresponding author
- Lamb, Bruce T
- ORCID
- Lamb, Bruce T
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2003-09
- Volume
- 24
- Issue
- 5
- Pages
- 645-653
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2164829288
- Cited by
- 55
- References
- 6
- Citations by year
- 2023: 3 · 2021: 1 · 2019: 1 · 2018: 1 · 2017: 4 · 2015: 2 · 2014: 3 · 2013: 6 · 2012: 3
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG14451, AG-08012, P50AG008012)
- National Cancer Institute (CA 43703, P30CA043703)
- National Institute of General Medical Sciences (GM-08613, T32GM008613)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta, amyloid precursor protein, Alzheimer's disease, APP processing, transgenic mouse model, Tg2576 mice, regional brain differences, hippocampus, cerebral cortex, APP mutations
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Ear, Enzyme-Linked Immunosorbent Assay, Eye, Female, Kidney, Male, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Olfactory Bulb, Pancreas, Peptide Fragments, Species Specificity, Testis, Tissue Distribution, Blotting, Western, Amyloid beta-Peptides, Mice
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