Amyloid neuropathology in the single Arctic APP transgenic model affects interconnected brain regions
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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Amyloid pathology might be gradually transmitted through connected brain structures.
“Some studies have indicated that amyloid pathology might be gradually transmitted through connected brain structures [10, 69, 84, 96], by mechanisms that are still under investigation.”
From Senescence-related impairment of autophagy induces toxic intraneuronal amyloid-β accumulation in a mouse model of amyloid pathology (2023) · cites this paper as [96]
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Self-citation
- 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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