Lifelong choline supplementation ameliorates Alzheimer’s disease pathology and associated cognitive deficits by attenuating microglia activation
Open accessAbstract
Currently, there are no effective therapies to ameliorate the pathological progression of Alzheimer's disease (AD). Evidence suggests that environmental factors may contribute to AD. Notably, dietary nutrients are suggested to play a key role in mediating mechanisms associated with brain function. Choline is a B‐like vitamin nutrient found in common foods that is important in various cell functions. It serves as a methyl donor and as a precursor for production of cell membranes. Choline is also the precursor for acetylcholine, a neurotransmitter which activates the alpha7 nicotinic acetylcholine receptor (α7nAchR), and also acts as an agonist for the Sigma‐1 R (σ1R). These receptors regulate CNS immune response, and their dysregulation contributes to AD pathogenesis. Here, we tested whether dietary choline supplementation throughout life reduces AD‐like pathology and rescues memory deficits in the APP/PS1 mouse model of AD. We exposed female APP/PS1 and NonTg mice to either a control choline (1.1 g/kg choline chloride) or a choline‐supplemented diet (5.0 g/kg choline chloride) from 2.5 to 10 months of age. Mice were tested in the Morris water maze to assess spatial memory followed by neuropathological evaluation. Lifelong choline supplementation significantly reduced amyloid‐β plaque load and improved spatial memory in APP/PS1 mice. Mechanistically, these changes were linked to a decrease of the amyloidogenic processing of APP, reductions in disease‐associated microglial activation, and a downregulation of the α7nAch and σ1 receptors. Our results demonstrate that lifelong choline supplementation produces profound benefits and suggest that simply modifying diet throughout life may reduce AD pathology.
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Lifelong choline supplementation has shown protective effects against Aβ pathology and microglial activation in female APP/PS1 mice.
“Lifelong choline supplementation has shown protective effects against Aβ pathology and microglial activation in female APP/PS1 mice.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [673]
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- Authors
- Velazquez, R., Ferreira, E., Knowles, S., Fux, C., Rodin, A., Winslow, W., & Oddo, S.
- Affiliations
- Arizona State University‐Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University Tempe AZ USA
- Arizona State University (US)
- Corresponding author
- Oddo, Salvatore
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2019-09-27
- Volume
- 18
- Issue
- 6
- Pages
- e13037-e13037
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC6826123
- OpenAlex
- W2976860431
- Cited by
- 156
- References
- 44
- Citations by year
- 2026: 10 · 2025: 26 · 2024: 32 · 2023: 32 · 2022: 27 · 2021: 23 · 2020: 5 · 2019: 1
- FWCI
- 9.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Aging Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (2R01AG037637‐07)
- National Science Foundation (1606833)
- 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
- choline supplementation, Alzheimer's disease, microglial activation, APP/PS1 mice, amyloid plaques, spatial memory impairment, alpha7 nicotinic acetylcholine receptor, sigma-1 receptor, dietary nutrients, neuroinflammation
- MeSH terms
- Alzheimer Disease, Animals, Brain, Choline, Longevity, Mice, Transgenic, Microglia, Nootropic Agents, Maze Learning, Dietary Supplements, Mice, Cognitive Dysfunction
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