Statins reduce the neurofibrillary tangle burden in a mouse model of tauopathy
Abstract
Statin treatment has been associated with a reduced risk of Alzheimer disease and decreased amyloid deposition in mouse models. No animal studies have reported effects of statins on tau aggregates and neurofibrillary tangles (NFTs), the pathological hallmarks of Alzheimer disease that correlate with dementia. We investigated the effect of statins on NFTs in a transgenic mouse tauopathy model and found the following: 1) 1-month treatment with the blood-brain barrier-permeable agent simvastatin in normocholesterolemic aged mice significantly reduced the NFT burden and decreased lectin-positive microglia; 2) simvastatin significantly decreased NFTs and improved T-maze performance in young animals treated for 8 months; 3) treatment of hypercholesterolemic mice for 5 months with blood-brain barrier-impermeable atorvastatin markedly reduced the NFT burden and decreased lectin-positive microglia; 4) nonstatin cholesterol-lowering strategies showed a modest NFT decrease compared with statin treatment; and 5) there was a positive correlation between microglial and NFT burden (r = 0.8). Together, these results suggest that statins reduce NFT burden irrespective of blood-brain barrier permeability at both early and late ages in long- and short-term treatment paradigms and under normocholesterolemic and hypercholesterolemic conditions. The decrease in microglia, coupled with the limited effect of nonstatin cholesterol lowering, suggests that the anti-NFT effect of statins may be related…
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Several studies have demonstrated that statin-mediated RhoA/ROCK inhibition reduces NFT formation and decreases Aβ production.
“Indeed, several studies have demonstrated that statin-mediated RhoA/ROCK inhibition reduces NFT formation and decreases Aβ production [182,183,187,224].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [224]
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- Authors
- Boimel, M., Grigoriadis, N., Lourbopoulos, A., Touloumi, O., Rosenmann, D., Abramsky, O., & Rosenmann, H.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Corresponding author
- Rosenmann, Hanna
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-03
- Volume
- 68
- Issue
- 3
- Pages
- 314-325
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W2014942056
- Cited by
- 86
- References
- 52
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 8 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 7 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 4 · 2013: 8 · 2012: 6
- FWCI
- 5.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- statins, neurofibrillary tangles, tauopathy, Alzheimer's disease, simvastatin, atorvastatin, microglia, blood-brain barrier permeability, hypercholesterolemia, cholesterol-lowering therapy, anti-inflammatory activity, transgenic mouse model, cognitive performance
- MeSH terms
- Atorvastatin, Ezetimibe, Animals, Azetidines, Brain, Capillary Permeability, Diet, Disease Models, Animal, Heptanoic Acids, Hypercholesterolemia, Immunohistochemistry, Mice, Transgenic, Pyrroles, Spinal Cord, Neurofibrillary Tangles, Maze Learning, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Simvastatin, Tauopathies, Mice
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