Cited by 127Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Amyloid-β pathology is attenuated by tauroursodeoxycholic acid treatment in APP/PS1 mice after disease onset

Dionísio, Pedro A., Amaral, Joana D., Ribeiro, Maria F., Lo, Adrian C., D'Hooge, Rudi, Rodrigues, Cecília M.P.·2015·Neurobiology of Aging

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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Crossref · 10.1016/j.neurobiolaging.2014.08.034

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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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