Cited by 125Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Intraneuronal APP/Aβ Trafficking and Plaque Formation in β‐Amyloid Precursor Protein and Presenilin‐1 Transgenic Mice

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Wirths, Oliver, Multhaup, Gerd, Czech, Christian, Feldmann, Nicole, Blanchard, Véronique, Tremp, Günter, Beyreuther, Konrad, Pradier, Laurent +1 more·2002·Brain Pathology

Abstract

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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Crossref · 10.1111/j.1750-3639.2002.tb00442.x

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  1. [45]45. Scheuermann S, Hambsch B, Hesse L, Stumm J, Schmidt C, Beher D, Bayer TA, Beyreuther K, Multhaup G (2001) Homodimerization of APP and its implication in the amyloidogenic pathway of Alzheimers disease. J Biol Chem 276:33923–33929. [DOI] [PubMed] [Google Scholar]

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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
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
Locations
  • Brain Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Alzheimer Forschung Initiative
  • Fritz Thyssen Stiftung
Topics
  • Health Sciences › Medicine › Physiology › 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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