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Intraneuronal Aβ Causes the Onset of Early Alzheimer’s Disease-Related Cognitive Deficits in Transgenic Mice
Open accessAbstract
Progressive memory loss and cognitive dysfunction are the hallmark clinical features of Alzheimer's disease (AD). Identifying the molecular triggers for the onset of AD-related cognitive decline presently requires the use of suitable animal models, such as the 3xTg-AD mice, which develop both amyloid and tangle pathology. Here, we characterize the onset of learning and memory deficits in this model. We report that 2-month-old, prepathologic mice are cognitively unimpaired. The earliest cognitive impairment manifests at 4 months as a deficit in long-term retention and correlates with the accumulation of intraneuronal Abeta in the hippocampus and amygdala. Plaque or tangle pathology is not apparent at this age, suggesting that they contribute to cognitive dysfunction at later time points. Clearance of the intraneuronal Abeta pathology by immunotherapy rescues the early cognitive deficits on a hippocampal-dependent task. Reemergence of the Abeta pathology again leads to cognitive deficits. This study strongly implicates intraneuronal Abeta in the onset of cognitive dysfunction.
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“In the 3XTg-AD mouse model (Oddo et al., 2003), long-term retention memory deficits in the Morris water maze correlate with intraneuronal A at 4 months, an age when mice do not have amyloid deposits (Billings et al., 2005).”
BackgroundRETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
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RetractedThe amyloid state and its association with protein misfolding diseases.
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Self-citation
Metadata
- Authors
- Billings, L. M., Oddo, S., Green, K. N., McGaugh, J. L., & LaFerla, F. M.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- LaFerla, Frank M.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 45
- Issue
- 5
- Pages
- 675-688
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1973276273
- Cited by
- 1,294
- References
- 47
- Citations by year
- 2026: 29 · 2025: 47 · 2024: 55 · 2023: 55 · 2022: 46 · 2021: 61 · 2020: 75 · 2019: 62 · 2018: 55 · 2017: 56 · 2016: 64 · 2015: 59 · 2014: 72 · 2013: 68 · 2012: 65
- FWCI
- 40.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute on Aging (AG0212982, F32AG024035, F32 AG24035-01)
- National Institute of Mental Health (MH12526)
- 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
- intraneuronal amyloid-beta, Alzheimer's disease, 3xTg-AD mice, learning and memory impairment, long-term memory retention, hippocampus, amygdala, amyloid plaques, neurofibrillary tangles, immunotherapy, animal models of Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Animals, Cognition Disorders, Female, Hippocampus, Male, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Amyloid beta-Peptides, Mice
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