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Intracellular Aβ and cognitive deficits precede β-amyloid deposition in transgenic arcAβ mice
Abstract
The brain pathology of Alzheimer's disease is characterized by abnormally aggregated Abeta in extracellular beta-amyloid plaques and along blood vessel walls, but the relation to intracellular Abeta remains unclear. To address the role of intracellular Abeta deposition in vivo, we expressed human APP with the combined Swedish and Arctic mutations in mice (arcAbeta mice). Intracellular punctate deposits of Abeta occurred concomitantly with robust cognitive impairments at the age of 6 months before the onset of beta-amyloid plaque formation and cerebral beta-amyloid angiopathy. beta-Amyloid plaques from arcAbeta mice had distinct dense-core morphologies with blood vessels appearing as seeding origins, suggesting reduced clearance of Abeta across blood vessels in arcAbeta mice. The co-incidence of intracellular Abeta deposits with behavioral deficits support an early role of intracellular Abeta in the pathophysiological cascade leading to beta-amyloid formation and functional impairment.
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“Furthermore, several AD Tg animal models are characterized by early and massive intraneuronal accumulation of Ab oligomers, loss of synaptic proteins, and behavioral impairment which occur in the absence of extracellular Ab plaques.7,51”
From Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration (2013) · cites this paper as [51]
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“FAD transgenic mouse models with the highest level of amyloidogenic Aβ display particularly prominent early intraneuronal Aβ accumulation [89, 106, 196].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [89]
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Intracellular amyloid-β in Alzheimer's disease
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Metadata
- Authors
- Knobloch, M., Konietzko, U., Krebs, D. C., & Nitsch, R. M.
- Affiliations
- University of Zurich (CH)
- Corresponding author
- Nitsch, Roger M.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2007-09
- Volume
- 28
- Issue
- 9
- Pages
- 1297-1306
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2006696380
- Cited by
- 259
- References
- 38
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 15 · 2023: 15 · 2022: 17 · 2021: 10 · 2020: 11 · 2019: 7 · 2018: 11 · 2017: 10 · 2016: 20 · 2015: 15 · 2014: 12 · 2013: 11 · 2012: 17
- FWCI
- 7.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (3200B0-112616)
- European Commission (6027, LSHM-CT-2003-503330)
- nccr – on the move
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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
- Alzheimer's disease, APP transgenic mice, cognitive impairment, amyloid plaques, cerebral amyloid angiopathy, amyloid clearance, amyloid seeding, APP mutations
- MeSH terms
- Age Factors, Analysis of Variance, Animals, Avoidance Learning, Behavior, Animal, Cognition Disorders, Exploratory Behavior, Humans, Mice, Inbred C57BL, Mice, Transgenic, Motor Activity, Mutation, Neurologic Examination, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Maze Learning, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Rotarod Performance Test, Mice, Plaque, Amyloid
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