Cited by 43Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Amyloid neuropathology in the single Arctic APP transgenic model affects interconnected brain regions

Rönnbäck, Annica, Sagelius, Hanna, Bergstedt, Karin Dillner, Näslund, Jan, Westermark, Gunilla T., Winblad, Bengt, Graff, Caroline·2012·Neurobiology of Aging

Abstract

The Arctic APP mutation (E693G) within the amyloid β (Aβ) domain of amyloid precursor protein (APP) leads to dementia with clinical features similar to Alzheimer's disease (AD), which is believed to be mediated via increased formation of protofibrils. We have generated a transgenic mouse model, TgAPParc, with neuron-specific expression of human amyloid precursor protein with the Arctic mutation (hAPParc), showing mild amyloid pathology with a relatively late onset. Here we performed a detailed analysis of the spatiotemporal progression of neuropathology in homozygous TgAPParc, focusing on intracellular Aβ and diffuse Aβ aggregates rather than amyloid plaques. We show that the neuropathology in homozygous TgAPParc mice starts with intracellular Aβ aggregates, which is followed by diffuse extracellular Aβ deposits in subiculum that later expands to brain regions receiving neuronal projections from regions already affected. Together this suggests that the pathology in TgAPParc mice affects interconnected brain regions and may represent a valuable tool to study the spread and progression of neuropathology in Alzheimer's disease.

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Crossref · 10.1016/j.neurobiolaging.2011.07.012

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Authors
Rönnbäck, A., Sagelius, H., Bergstedt, K. D., Näslund, J., Westermark, G. T., Winblad, B., & Graff, C.
Affiliations
  • Karolinska Institutet (SE)
  • Uppsala University (SE)
Corresponding author
Rönnbäck, Annica
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2012-04
Volume
33
Issue
4
Pages
831.e11-831.e19
ISSN
0197-4580 (ISSN-L)
OpenAlex
W2096347759
Cited by
43
References
47
Citations by year
2025: 1 · 2024: 1 · 2023: 3 · 2021: 1 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 5 · 2014: 4 · 2013: 3 · 2012: 5
FWCI
2.62
Type
journal article
Language
en
Open access
closed
Locations
  • Neurobiology of Aging (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Dainippon Sumitomo Pharma
  • Karolinska Institutet
  • Knut och Alice Wallenbergs Stiftelse
  • University of California, Irvine
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 precursor protein, Alzheimer's disease, transgenic mouse model, subiculum, dementia, amyloid protofibrils
MeSH terms
Age Factors, Alzheimer Disease, Analysis of Variance, Animals, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Female, Hippocampus, Humans, Male, Mice, Transgenic, Mutation, Peptide Fragments, Amyloid beta-Peptides, Microscopy, Immunoelectron, Amyloid beta-Protein Precursor, Mice

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