Amyloid β induces interneuron-specific changes in the hippocampus of APPNL-F mice
Open accessAbstract
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and amyloid-beta (Aβ) depositions generated by the proteolysis of amyloid precursor protein (APP) in the brain. In APPNL-F mice, APP gene was humanized and contains two familial AD mutations, and APP-unlike other mouse models of AD-is driven by the endogenous mouse APP promoter. Similar to people without apparent cognitive dysfunction but with heavy Aβ plaque load, we found no significant decline in the working memory of adult APPNL-F mice, but these mice showed decline in the expression of normal anxiety. Using immunohistochemistry and 3D block-face scanning electron microscopy, we found no changes in GABAA receptor positivity and size of somatic and dendritic synapses of hippocampal interneurons. We did not find alterations in the level of expression of perineuronal nets around parvalbumin (PV) interneurons or in the density of PV- or somatostatin-positive hippocampal interneurons. However, in contrast to other investigated cell types, PV interneuron axons were occasionally mildly dystrophic around Aβ plaques, and the synapses of PV-positive axon initial segment (AIS)-targeting interneurons were significantly enlarged. Our results suggest that PV interneurons are highly resistant to amyloidosis in APPNL-F mice and amyloid-induced increase in hippocampal pyramidal cell excitability may be compensated by PV-positive AIS-targeting cells. Mechanisms that make PV neurons more resilient could therefore be exploited in the treatment of AD for mitigating Aβ-related inflammatory effects on neurons.
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The Tg2576/APPsw and APPNL-F mouse lines of amyloidosis showed no change in hippocampal PNN abundance or distribution compared to controls.
“while the Tg2576/APPsw and APPNL-F mouse lines of amyloidosis showed no change in hippocampal PNN abundance or distribution compared to controls (Morawski et al. 2010b; Sos et al. 2020).”
From Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration (2024) · cites this paper as Sos et al. 2020
The Results section, “PV IN-specific perineuronal nets do not change in APPNL-F mice” (page unavailable), reports no evidence of PNN deterioration in a qualitative comparison of APPNL-F mice and WT littermates. That supports unchanged PNN coverage around hippocampal PV neurons, but the paper does not establish unchanged PNN abundance or distribution throughout the hippocampus. The Tg2576/APPsw line is separately cited to Morawski et al., so it is not assessed against Sos et al. (LLM, conf=0.84)
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The Bidirectional Relationship Between Epilepsy and Alzheimer’s Disease
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Somatostatin slows Aβ plaque deposition in aged APPNL-F/NL-F mice by blocking Aβ aggregation
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Linking Social Cognition, Parvalbumin Interneurons, and Oxytocin in Alzheimer’s Disease: An Update
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Amyloid Pathology Impairs Experience-Dependent Inhibitory Synaptic Plasticity
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- Authors
- Sos, K. E., Mayer, M. I., Takács, V. T., Major, A., Bardóczi, Z., Beres, B. M., Szeles, T., Saito, T., Saido, T. C., Mody, I., Freund, T. F., & Nyiri, G.
- Affiliations
- Semmelweis University (HU)
- HUN-REN Institute of Experimental Medicine (HU)
- RIKEN Center for Brain Science (JP)
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2020-05-29
- Volume
- 15
- Issue
- 5
- Pages
- e0233700
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC7259556
- OpenAlex
- W3030131565
- Cited by
- 37
- References
- 126
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 6 · 2021: 8
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- creativecommons.org/publicdomain/zero/1.0/ (vor)
- Locations
- PLoS ONE (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Foundation for the National Institutes of Health (NS030549)
- Nemzeti Kutatási, Fejlesztési és Innovaciós Alap (OTKA K119521, OTKA NN125643, VKSZ_14-1-2O15-0155)
- Hungarian Brain Research Program (2017-1.2.1-NKP-2017-00002)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta, Alzheimer's disease, parvalbumin interneurons, hippocampus, anxiety, GABAA receptor, synapse size, axon initial segment, perineuronal nets, somatostatin interneurons, amyloid plaques
- MeSH terms
- Alzheimer Disease, Animals, Axons, Hippocampus, Humans, Interneurons, Memory, Short-Term, Mice, Transgenic, Mutation, Nerve Net, Peptide Fragments, Receptors, GABA-A, Amyloid beta-Peptides, Pyramidal Cells, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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