5XFAD Mice Show Early Onset Gap Detection Deficits
Open accessAbstract
Alzheimer's patients show auditory temporal processing deficits very early in disease progression, before the onset of major cognitive impairments. In addition to potentially contributing to speech perception and communication deficits in patients, this also represents a potential early biomarker for Alzheimer's. For this reason, tests of temporal processing such as gap detection have been proposed as an early diagnosis tool. For a biomarker such as gap detection deficits to have maximum clinical value, it is important to understand what underlying neuropathology it reflects. For example, temporal processing deficits could arise from alterations at cortical, midbrain, or brainstem levels. Mouse models of Alzheimer's disease can provide the ability to reveal in detail the molecular and circuit pathology underlying disease symptoms. Here we tested whether 5XFAD mice, a leading Alzheimer's mouse model, exhibit impaired temporal processing. We found that 5XFAD mice showed robust gap detection deficits. Gap detection deficits were first detectable at about 2 months of age and became progressively worse, especially for males and for longer gap durations. We conclude that 5XFAD mice are well-suited to serve as a model for understanding the circuit mechanisms that contribute to Alzheimer's-related gap detection deficits.
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The 5XFAD mouse model recapitulates many phenotypes of AD pathology in a quick and progressive manner.
“The 5XFAD mouse model of AD was used throughout the study as the expression of human transgenes, amyloid precursor protein (APP) and presenilin 1 (PSEN1), recapitulate many of the phenotypes of the AD pathology at a quick and progressive manner [17, 18].”
From Control of the temporal development of Alzheimer’s disease pathology by the MR1/MAIT cell axis (2023) · cites this paper as [18]
The Introduction reports early amyloid deposition, neurodegeneration and cognitive deficits in 5XFAD mice, and the Discussion describes early, aggressive amyloid pathology. This supports the claim of rapid development of several AD-related phenotypes. Our copy describes five human Alzheimer’s mutations but does not identify APP and PSEN1 as the transgenes named in the citing sentence. (LLM, conf=0.85)
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“We opted to test gap detection in 5XFAD mice because these mice show early and aggressive amyloid pathology (Oakley et al., 2006).”
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Sex differences in Alzheimer's disease and other dementias
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Cited by
Sorted by citations
Control of the temporal development of Alzheimer’s disease pathology by the MR1/MAIT cell axis
Wyatt-Johnson, S. K., Kersey, H. N., Codocedo, J. F., Newell, K. L., Landreth, G. E., Lamb, B. T., Oblak, A. L., & Brutkiewicz, R. R. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02761-6 · Cited by 22 · see citing works
“Animals and ethics statements The 5XFAD mouse model of AD was used throughout the study as the expression of human transgenes, amyloid precursor protein (APP) and presenilin 1 (PSEN1), recapitulate many of the phenotypes of the AD pathology at a quick and progressive manner [17, 18].”
Method
- Authors
- Kaylegian, K., Stebritz, A. J., Weible, A. P., & Wehr, M.
- Affiliations
- University of Oregon (US)
- Corresponding author
- Wehr, Michael
- Venue
- Frontiers in Aging Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2019-04-02
- Volume
- 11
- Pages
- 66-66
- ISSN
- 1663-4365 (ISSN-L)
- PMC
- PMC6454034
- OpenAlex
- W2929625587
- Cited by
- 20
- References
- 4
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 1
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Aging Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institute on Deafness and Other Communication Disorders (R01 DC-015828)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hearing Loss and Rehabilitation
- Keywords
- 5xFAD mice, Alzheimer's disease, auditory temporal processing, early biomarkers, mouse models of Alzheimer's disease, sex differences, gap duration
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