TUDCA, a Bile Acid, Attenuates Amyloid Precursor Protein Processing and Amyloid-β Deposition in APP/PS1 Mice
Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by accumulation of amyloid-β (Aβ) peptide in the hippocampus and frontal cortex of the brain, leading to progressive cognitive decline. The endogenous bile acid tauroursodeoxycholic acid (TUDCA) is a strong neuroprotective agent in several experimental models of disease, including neuronal exposure to Aβ. Nevertheless, the therapeutic role of TUDCA in AD pathology has not yet been ascertained. Here we report that feeding APP/PS1 double-transgenic mice with diet containing 0.4 % TUDCA for 6 months reduced accumulation of Aβ deposits in the brain, markedly ameliorating memory deficits. This was accompanied by reduced glial activation and neuronal integrity loss in TUDCA-fed APP/PS1 mice compared to untreated APP/PS1 mice. Furthermore, TUDCA regulated lipid-metabolism mediators involved in Aβ production and accumulation in the brains of transgenic mice. Overall amyloidogenic APP processing was reduced with TUDCA treatment, in association with, but not limited to, modulation of γ-secretase activity. Consequently, a significant decrease in Aβ(1-40) and Aβ(1-42) levels was observed in both hippocampus and frontal cortex of TUDCA-treated APP/PS1 mice, suggesting that chronic feeding of TUDCA interferes with Aβ production, possibly through the regulation of lipid-metabolism mediators associated with APP processing. These results highlight TUDCA as a potential therapeutic strategy for the prevention and treatment of AD.
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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 [374]
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[Retracted] A Review of Bile Acid Metabolism and Signaling in Cognitive Dysfunction‐Related Diseases
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Retracted
- Authors
- Nunes, A. F., Amaral, J. D., Lo, A. C., Fonseca, M. B., Viana, R. J. S., Callaerts-Vegh, Z., D’Hooge, R., & Rodrigues, C. M. P.
- Affiliations
- University of Lisbon (PT)
- KU Leuven (BE)
- Corresponding author
- Rodrigues, Cecília M. P.
- Venue
- Molecular Neurobiology
- Published
- 2012-03-23
- Volume
- 45
- Issue
- 3
- Pages
- 440-454
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W2005971787
- Cited by
- 192
- References
- 55
- Citations by year
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- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Keywords
- tauroursodeoxycholic acid, bile acids, Alzheimer's disease, amyloid-beta deposition, APP/PS1 mice, APP processing, gamma-secretase, lipid metabolism, glial activation, memory impairment, neuroprotection, dietary supplementation
- MeSH terms
- Alzheimer Disease, Animals, Astrocytes, Bile Acids and Salts, Brain, Cognition Disorders, DNA-Binding Proteins, Humans, Mice, Transgenic, Nerve Tissue Proteins, Neurons, Nuclear Proteins, Protein Processing, Post-Translational, Taurochenodeoxycholic Acid, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Microglia, Lipid Metabolism, Mice, Synucleins, Presenilin-1
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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