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Intraneuronal APP/Aβ Trafficking and Plaque Formation in β‐Amyloid Precursor Protein and Presenilin‐1 Transgenic Mice
Open accessAbstract
Neuropil deposition of beta-amyloid peptides A beta40 and A beta42 is believed to be the key event in the neurodegenerative processes of Alzheimer's disease (AD). Since A beta seems to carry a transport signal that is required for axonal sorting of its precursor beta-amyloid precursor protein (APP), we studied the intraneuronal staining profile of A beta peptides in a transgenic mouse model expressing human mutant APP751 (KM670/671NL and V7171) and human mutant presenilin-1 (PS-1 M146L) in neurons. Using surface plasmon resonance we analyzed the A beta antibodies and defined their binding profile to APP, A beta40 and A beta42. Immunohistochemical staining revealed that intraneuronal A beta40 and A beta42 staining preceded plaque deposition, which started at 3 months of age. A beta was observed in the somatodendritic and axonal compartments of many neurons. Interestingly, the striatum, which lacks transgenic APP expression harbored many plaques at 10 months of age. This is most likely due to an APP/A beta transport problem and may be a model region to study APP/A beta trafficking as an early pathological event.
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Metadata
- Authors
- Wirths, O., Multhaup, G., Czech, C., Feldmann, N., Blanchard, V., Tremp, G., Beyreuther, K., Pradier, L., & Bayer, T. A.
- Affiliations
- University of Bonn (DE)
- Heidelberg University (DE)
- Sanofi (France) (FR)
- Corresponding author
- Bayer, Thomas A.
- Venue
- Brain Pathology
- Publisher
- Wiley
- Published
- 2002-07
- Volume
- 12
- Issue
- 3
- Pages
- 275-286
- ISSN
- 1015-6305 (ISSN-L)
- 1750-3639
- PMC
- PMC8095864
- OpenAlex
- W1971608812
- Cited by
- 125
- References
- 64
- Citations by year
- 2025: 4 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 6 · 2019: 1 · 2018: 5 · 2017: 2 · 2016: 7 · 2015: 6 · 2014: 5 · 2013: 6 · 2012: 9
- FWCI
- 5.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer Forschung Initiative
- Fritz Thyssen Stiftung
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- amyloid-beta, amyloid precursor protein, presenilin 1, Alzheimer's disease, amyloid plaques, Aβ40, amyloid-beta 42, axonal transport, striatum, surface plasmon resonance
- MeSH terms
- Alzheimer Disease, Animals, Antibodies, Brain, Immunohistochemistry, Membrane Proteins, Mice, Transgenic, Mutation, Neurons, Time Factors, Blotting, Western, Polymerase Chain Reaction, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Surface Plasmon Resonance, Protein Transport, Mice, Presenilin-1, Plaque, Amyloid
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