Cited by 259Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Intracellular Aβ and cognitive deficits precede β-amyloid deposition in transgenic arcAβ mice

Knobloch, Marlen, Konietzko, Uwe, Krebs, Danielle C., Nitsch, Roger M.·2007·Neurobiology of Aging

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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Crossref · 10.1016/j.neurobiolaging.2006.06.019

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38 of 38 references verified0 citation errors · 0 not checkable

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  • Several AD Tg animal models are characterized by early and massive intraneuronal accumulation of Aβ oligomers, loss of synaptic proteins, and behavioral impairment which occur in the absence of extracellular Aβ plaques.

    “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”
  • FAD transgenic mouse models with the highest level of amyloidogenic Aβ display particularly prominent early intraneuronal Aβ accumulation.

    “FAD transgenic mouse models with the highest level of amyloidogenic Aβ display particularly prominent early intraneuronal Aβ accumulation [89, 106, 196].”

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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
  • 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
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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