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
Open accessAbstract
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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In the citing paper
“In the E693Delta APP mutation discovered in a Japanese kindred (Nishitsuji et al., 2009), the presence of intracellular oligomers is essentially identical in patients and in the transgenic mouse model (Tomiyama et al., 2010).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Tomiyama et al., 2010
In the citing paper
“This idea is confirmed by studies reporting a transgenic mouse model bearing APP with a recently described AD-associated mutation that exhibits intraneuronal Aβ accumulation in the absence of plaques and still shows signs of AD-related neurodegeneration [113].”
From Senescence-related impairment of autophagy induces toxic intraneuronal amyloid-β accumulation in a mouse model of amyloid pathology (2023) · cites this paper as [113]
In the citing paper
“The other major limitation of these mouse models was that while some showed evidence of localized hyperphosphylated tau that may represent “pretangles”[107, 118, 151, 159], none developed neurofibrillary tangles.”
From Alzheimer's disease: experimental models and reality (2017) · cites this paper as [159]
In the citing paper
“The APP E693Δ-Tg model expresses the Osaka (APPE693Δ) mutation, which results in a unique phenotype of significantly increased expression of Aβ oligomers, synaptic impairment and cognitive impairments from 8 months of age, but no plaque or tau pathology formation [159].”
From Alzheimer's disease: experimental models and reality (2017) · cites this paper as [159]
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1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
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“The finding that A oligomers were largely recovered in insoluble fractions suggests the possibility that intraneuronal A in the APPE693 -Tg mice may form fibrils, as reported in other APP-Tg mice (Casas et al., 2004; Oakley et al., 2006).”
BackgroundMethodResultInfluentialDiffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins
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Natural oligomers of the amyloid-β protein specifically disrupt cognitive function
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MethodIntraneuronal Aβ42 Accumulation in Human Brain
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MethodImmunization reverses memory deficits without reducing brain Aβ burden in Alzheimer's disease model
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Self-citationAlzheimer's disease-type neuronal tau hyperphosphorylation induced by Aβ oligomers
De Felice, F. G., Wu, D., Lambert, M. P., Fernandez, S. J., Velasco, P. T., Lacor, P. N., Bigio, E. H., Jerecic, J., Acton, P. J., Shughrue, P. J., et al. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.02.029 · Cited by 432
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BackgroundAlzheimer disease models and human neuropathology: similarities and differences
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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)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-04-06
- Volume
- 30
- Issue
- 14
- Pages
- 4845-4856
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6632783
- OpenAlex
- W2095031277
- Semantic Scholar
- 599d4363741ebd4649dc5b7f2de2da4503720038
- 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
- hybrid
- doi.org
- Licence
- 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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