Cited by 396Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.

A Mouse Model of Amyloid β Oligomers: Their Contribution to Synaptic Alteration, Abnormal Tau Phosphorylation, Glial Activation, and Neuronal Loss In Vivo

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Abstract

Although amyloid β (Aβ) oligomers are presumed to cause synaptic and cognitive dysfunction in Alzheimer's disease (AD), their contribution to other pathological features of AD remains unclear. To address the latter, we generated APP transgenic mice expressing the E693Δ mutation, which causes AD by enhanced Aβ oligomerization without fibrillization. The mice displayed age-dependent accumulation of intraneuronal Aβ oligomers from 8 months but no extracellular amyloid deposits even at 24 months. Hippocampal synaptic plasticity and memory were impaired at 8 months, at which time the presynaptic marker synaptophysin began to decrease. Furthermore, we detected abnormal tau phosphorylation from 8 months, microglial activation from 12 months, astrocyte activation from 18 months, and neuronal loss at 24 months. These findings suggest that Aβ oligomers cause not only synaptic alteration but also other features of AD pathology and that these mice are a useful model of Aβ oligomer-induced pathology in the absence of amyloid plaques.

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Crossref · 10.1523/jneurosci.5825-09.2010

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Metadata

Authors
Tomiyama, T., Matsuyama, S., Iso, H., Umeda, T., Takuma, H., Ohnishi, K., Ishibashi, K., Teraoka, R., Sakama, N., Yamashita, T., Nishitsuji, K., Ito, K., Shimada, H., Lambert, M. P., Klein, W. L., & Mori, H.
Affiliations
  • Osaka City University (JP)
  • Himeji Dokkyo University (JP)
  • Hyogo University of Health Sciences (JP)
  • Northwestern University (US)
Venue
The Journal of Neuroscience
Published
2010-04-06
Volume
30
Issue
14
Pages
4845-4856
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2095031277
Cited by
396
References
52
Citations by year
2026: 3 · 2025: 13 · 2024: 21 · 2023: 26 · 2022: 20 · 2021: 24 · 2020: 21 · 2019: 23 · 2018: 20 · 2017: 19 · 2016: 18 · 2015: 33 · 2014: 22 · 2013: 27 · 2012: 39
FWCI
28.82
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Alzheimer's Association (IIRG-09-132098)
  • Ministry of Education, Culture, Sports, Science and Technology (18023033, 17300114, 20023026, IIRG-09-132098)
  • Ministry of Health, Labour and Welfare
  • Japan Society for the Promotion of Science (18023033, 20023026, 17300114)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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 oligomers, Alzheimer's disease, APP transgenic mice, synaptic plasticity, memory impairment, synaptophysin, tau phosphorylation, microglial activation, astrocyte activation, neuronal loss, mouse model
MeSH terms
Alzheimer Disease, Animals, Disease Models, Animal, Humans, Male, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Transgenic, Neuroglia, Neurons, Phosphorylation, Synapses, Amyloid beta-Peptides, tau Proteins, Cell Death, Mice

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