Amyloid-β pathology is attenuated by tauroursodeoxycholic acid treatment in APP/PS1 mice after disease onset
Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder hallmarked by the accumulation of extracellular amyloid-β (Aβ) peptide and intraneuronal hyperphosphorylated tau, as well as chronic neuroinflammation. Tauroursodeoxycholic acid (TUDCA) is an endogenous anti-apoptotic bile acid with potent neuroprotective properties in several experimental models of AD. We have previously reported the therapeutic efficacy of TUDCA treatment before amyloid plaque deposition in APP/PS1 double-transgenic mice. In the present study, we evaluated the protective effects of TUDCA when administrated after the onset of amyloid pathology. APP/PS1 transgenic mice with 7 months of age were injected intraperitoneally with TUDCA (500 mg/kg) every 3 days for 3 months. TUDCA treatment significantly attenuated Aβ deposition in the brain, with a concomitant decrease in Aβ₁₋₄₀ and Aβ₁₋₄₂ levels. The amyloidogenic processing of amyloid precursor protein was also reduced, indicating that TUDCA interferes with Aβ production. In addition, TUDCA abrogated GSK3β hyperactivity, which is highly implicated in tau hyperphosphorylation and glial activation. This effect was likely dependent on the specific activation of the upstream kinase, Akt. Finally, TUDCA treatment decreased glial activation and reduced proinflammatory cytokine messenger RNA expression, while partially rescuing synaptic loss. Overall, our results suggest that TUDCA is a promising therapeutic strategy not only for prevention but also for treatment of AD after disease onset.
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TUDCA treatment inhibits Aβ deposition and glial activation in APP/PS1 mice and HFD-fed A7-Tg mice.
“Notably, TUDCA treatment has demonstrated the ability to inhibit Aβ deposition and glial activation in APP/PS1 mice and HFD-fed A7-Tg mice.372–375”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [372]
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- Authors
- Dionísio, P. A., Amaral, J. D., Ribeiro, M. F., Lo, A. C., D'Hooge, R., & Rodrigues, C. M. P.
- Affiliations
- University of Lisbon (PT)
- KU Leuven (BE)
- Corresponding author
- Amaral, Joana D.
- Rodrigues, Cecília M.P.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 36
- Issue
- 1
- Pages
- 228-240
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2146454538
- Cited by
- 127
- References
- 64
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 23 · 2023: 11 · 2022: 8 · 2021: 11 · 2020: 16 · 2019: 7 · 2018: 8 · 2017: 7 · 2016: 8 · 2015: 4
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Fundação para a Ciência e a Tecnologia (PTDC/SAU-NMC/117877/2010)
- Fundação para a Ciência e a Tecnologia, Portugal (SFRH/BPD/47376/2008)
- 7FP
- MEMOSAD
- Federal Science fund FWO-Vlaanderen (G.0327.08)
- 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
- tauroursodeoxycholic acid, Alzheimer's disease, amyloid-beta, APP/PS1 mice, GSK3β, Akt signaling, tau hyperphosphorylation, glial activation, neuroinflammation, inflammatory cytokines, synaptic loss, APP processing
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Alzheimer Disease, Animals, Cholagogues and Choleretics, Disease Models, Animal, Mice, Transgenic, RNA, Messenger, Taurochenodeoxycholic Acid, Gene Expression, Cytokines, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, tau Proteins, Neuroprotective Agents, Inflammation Mediators, Glycogen Synthase Kinase 3, Presenilin-1, Molecular Targeted Therapy, Protein Aggregation, Pathological
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