Calcineurin inhibition with FK506 ameliorates dendritic spine density deficits in plaque-bearing Alzheimer model mice
Open accessAbstract
Synapse loss is the strongest correlate of cognitive decline in Alzheimer's disease, and synapses are an attractive therapeutic target due to their plastic nature that allows for potential recovery with intervention. We have previously demonstrated in transgenic mice that form senile plaques that dendrites surrounding plaques become dystrophic and lose postsynaptic dendritic spines. Furthermore, we found strong evidence that plaque-associated dendritic changes are mediated by calcineurin, a calcium-dependent phosphatase involved in cell signaling, using in vitro models and genetically encoded inhibitors in mouse models. In this study, we pharmacologically inhibited calcineurin with FK506 treatment to test the hypothesis that calcineurin inhibition will allow recovery of plaque-associated synapse loss. We found that in plaque bearing transgenic mice, short term (1 week) FK506 treatment results in an amelioration of dendritic spine loss. We also observe an effect on spine morphology in wild-type mice with FK506 treatment. These data show that systemic FK506 administration, and hence calcineurin inhibition, may be neuroprotective for amyloid beta induced synaptic alterations.
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Aβ-induced dendritic spine loss can be prevented with the calcineurin inhibitor FK506.
“Aβ-induced dendritic spine loss can be prevented with the calcineurin inhibitor FK506.20”
From Controlled Cortical Impact Results in an Extensive Loss of Dendritic Spines that Is Not Mediated by Injury-Induced Amyloid-Beta Accumulation (2013) · cites this paper as [20]
The Discussion reports that seven days of FK506 rescued dendritic spine density in APP/PS1 mice and describes this as improving Aβ-induced spine loss. The study tested recovery of an existing deficit in plaque-bearing mice, not whether FK506 prevents spine loss from occurring. (LLM, conf=0.82)
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- Authors
- Rozkalne, A., Hyman, B. T., & Spires-Jones, T. L.
- Affiliations
- Harvard University (US)
- Corresponding author
- Hyman, Bradley T.
- ORCID
- Hyman, Bradley T.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 41
- Issue
- 3
- Pages
- 650-654
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC3031746
- OpenAlex
- W2035302673
- Cited by
- 103
- References
- 35
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 11 · 2023: 12 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 4 · 2017: 10 · 2016: 5 · 2015: 7 · 2014: 6 · 2013: 7 · 2012: 4
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Alzheimer's Drug Discovery Foundation (AG08487, P50 AG005134)
- 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
- calcineurin inhibition, FK506, dendritic spine loss, Alzheimer's disease, amyloid plaques, synaptic loss, neuroprotection, transgenic mouse model, calcium-dependent phosphatase
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Mice, Transgenic, Tacrolimus, Dendritic Spines, Mice, Plaque, Amyloid, Calcineurin Inhibitors
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