Tau pathology does not affect experience-driven single-neuron and network-wide Arc/Arg3.1 responses
Open accessAbstract
Intraneuronal neurofibrillary tangles (NFTs) - a characteristic pathological feature of Alzheimer's and several other neurodegenerative diseases - are considered a major target for drug development. Tangle load correlates well with the severity of cognitive symptoms and mouse models of tauopathy are behaviorally impaired. However, there is little evidence that NFTs directly impact physiological properties of host neurons. Here we used a transgenic mouse model of tauopathy to study how advanced tau pathology in different brain regions affects activity-driven expression of immediate-early gene Arc required for experience-dependent consolidation of long-term memories. We demonstrate in vivo that visual cortex neurons with tangles are as likely to express comparable amounts of Arc in response to structured visual stimulation as their neighbors without tangles. Probability of experience-dependent Arc response was not affected by tau tangles in both visual cortex and hippocampal pyramidal neurons as determined postmortem. Moreover, whole brain analysis showed that network-wide activity-driven Arc expression was not affected by tau pathology in any of the brain regions, including brain areas with the highest tangle load. Our findings suggest that intraneuronal NFTs do not affect signaling cascades leading to experience-dependent gene expression required for long-term synaptic plasticity.
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Soluble tau, rather than fibrillar tau, impacts responsiveness of neurons to environmental stimuli in hippocampus after memory formation.
“From assessments of immediate early gene expression in the hippocampus after memory formation, it again appears that soluble tau, rather than fibrillar tau, seems to impact the responsiveness of neurons to environmental stimuli.”
From All the Tau We Cannot See (2023) · cites this paper as [22]
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- Authors
- Rudinskiy, N., Hawkes, J. M., Wegmann, S., Kuchibhotla, K. V., Muzikansky, A., Betensky, R. A., Spires-Jones, T. L., & Hyman, B. T.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Hyman, Bradley T
- Venue
- Acta Neuropathologica Communications
- Published
- 2014-06-10
- Volume
- 2
- Issue
- 1
- Pages
- 63-63
- ISSN
- 2051-5960 (ISSN-L)
- PMC
- PMC4229905
- OpenAlex
- W2123478580
- Cited by
- 32
- References
- 46
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 8 · 2021: 2 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 4 · 2015: 2 · 2014: 1
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Acta Neuropathologica Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- Harvard NeuroDiscovery Center
- Deutsche Forschungsgemeinschaft
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institutes of Health (AG005134, AG026249)
- Fidelity Biosciences
- National Institute on Aging (R01AG026249, AG005134, R00AG033670, AG026249, P50AG005134, R00AG33670)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- tau pathology, neurofibrillary tangles, Arc/Arg3.1, immediate early gene expression, visual cortex, hippocampal pyramidal neurons, synaptic plasticity, long-term memory consolidation
- MeSH terms
- AIDS-Related Complex, Animals, Brain, Disease Models, Animal, Gene Expression Regulation, Humans, Luminescent Proteins, Mice, Transgenic, Mutation, Neural Pathways, Neurons, Photic Stimulation, Neurofibrillary Tangles, tau Proteins, Tauopathies, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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