Dietary Cholesterol and Its Effect on Tau Protein: A Study in Apolipoprotein E-Deficient and P301L Human Tau Mice
Abstract
Apolipoprotein E (ApoE) is the major cholesterol transporter in the brain. There is epidemiological and experimental evidence for involvement of cholesterol metabolism in the development and progression of Alzheimer disease. A dietary effect on tau phosphorylation or aggregation, or a role of apoE in tau metabolism, has been studied experimentally, but the data are ambiguous. To elucidate the relationship between cholesterol and tau, we studied mice expressing P301L mutant human tau but not apoE (htau-ApoE) and P301L mice with wild-type ApoE (htau- ApoE); both genotypes develop neuron cytoskeletal changes similar to those found in Alzheimer disease. Mice were kept on a cholesterol-enriched diet or control diet for 15 weeks. The numbers of neurons with hyperphosphorylated and conformationally changed tau in the cerebral cortex were assessed by immunohistochemistry, and sterol levels were determined. Highly elevated dietary serum cholesterol levels enhanced ongoing tau pathology in htau-ApoE mice; this effect correlated with elevated brain cholesterol metabolite 27-hydroxycholesterol levels. Apolipoprotein E deficiency promoted significant increases of tau phosphorylation and conformational changes in mice on a control diet. In htau-ApoE mice on the high cholesterol regimen, brain oxysterol levels were less than in htau-ApoE mice, and the numbers of neurons with pathologically altered tau were similar to those in htau-ApoE mice on the high-cholesterol diet.
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Diets with increased cholesterol increase tau phosphorylation in wild-type and human tau transgenic mammals.
“Reports in both wild-type and in human tau transgenic mammals indicate that diets with increased cholesterol do indeed increase tau phosphorylation (265–267).”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [267]
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Background
- Authors
- Glöckner, F., Meske, V., Lütjohann, D., & Ohm, T. G.
- Affiliations
- University of Bonn (DE)
- Corresponding author
- Glöckner, Frauke
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-04
- Volume
- 70
- Issue
- 4
- Pages
- 292-301
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W1968579274
- Cited by
- 35
- References
- 72
- Citations by year
- 2024: 5 · 2023: 4 · 2022: 5 · 2021: 2 · 2020: 1 · 2019: 1 · 2017: 2 · 2016: 2 · 2014: 3 · 2013: 6 · 2012: 3
- FWCI
- 2.84
- 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
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- dietary cholesterol, tau protein, apolipoprotein E deficiency, Alzheimer's disease, tau phosphorylation, tau aggregation, 27-hydroxycholesterol, oxysterols, brain cholesterol metabolism, cholesterol-enriched diet, transgenic mouse model
- MeSH terms
- Animals, Apolipoproteins E, Brain Chemistry, Cell Count, Cholesterol, Cholesterol, Dietary, Diet, Genotype, Humans, Immunohistochemistry, Lipids, Mice, Transgenic, Phosphorylation, Protein Conformation, tau Proteins, Mice, Knockout, Mice
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