Cellular cholesterol homeostasis and Alzheimer’s disease
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) potential lipid-based therapeutic targets to treat AD. At the end, we recommend several research topics that we believe would help in better understanding the connection between cholesterol and AD for further investigations.
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It remains unclear how changes in plasma cholesterol might affect CNS sterol metabolism and cognitive function, and no evidence suggests a net transfer of sterols from the periphery to the CNS.
“However, it remains unclear how changes in plasma cholesterol might affect CNS sterol metabolism and if such changes affect cognitive function, and no evidence suggest a net transfer of sterols from the periphery to the CNS (Dietschy and Turley, 2004; Chang et al., 2017).”
From PCSK9 deficiency alters brain lipid composition without affecting brain development and function (2023) · cites this paper as Chang et al., 2017
In “AD and the involvement of cholesterol and ApoE4” (page not available), the review says blood-borne cholesterol does not readily equilibrate with brain cholesterol and that essentially all brain cholesterol is synthesized there. This supports limited peripheral-to-CNS cholesterol transfer, but not the broader assertion that there is no evidence of net transfer of any sterols; “Metabolites of cholesterol” describes possible movement of 27-hydroxycholesterol into the brain when the blood–brain barrier is leaky. The cited passages do not establish whether changes in plasma cholesterol affect CNS sterol metabolism or cognition. (LLM, conf=0.85)
Experimental — accuracy not yet measuredPeripheral and CNS cholesterol metabolism operate independently of each other.
“supporting the hypothesis that peripheral and CNS cholesterol metabolism operate independently of each other (Dietschy and Turley, 2004; Chang et al., 2017).”
From PCSK9 deficiency alters brain lipid composition without affecting brain development and function (2023) · cites this paper as Chang et al., 2017
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PCSK9 deficiency alters brain lipid composition without affecting brain development and function
Pärn, A., Olsen, D., Tuvikene, J., Kaas, M., Borisova, E., Bilgin, M., Elhauge, M., Vilstrup, J., Madsen, P., Ambrozkiewicz, M. C., et al. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1084633 · Cited by 16 · see citing works
Linden, A. K., Affaneh, A., Aylward, A., Wong, Y., Kessler, J. A., & Peng, C.-Y. (2025) · doi:10.64898/2025.12.14.694212 · Cited by 1 · see citing works
- Authors
- Chang, T.-Y., Yamauchi, Y., Hasan, M. T., & Chang, C.
- Affiliations
- Dartmouth College (US)
- Life Science Institute (JP)
- Achucarro Basque Center for Neuroscience (ES)
- Corresponding author
- Chang, Ta-Yuan
- Chang, Catherine
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 58
- Issue
- 12
- Pages
- 2239-2254
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC5711498
- OpenAlex
- W2603910820
- Cited by
- 155
- References
- 25
- Citations by year
- 2026: 15 · 2025: 14 · 2024: 15 · 2023: 22 · 2022: 20 · 2021: 17 · 2020: 18 · 2019: 15 · 2018: 14 · 2017: 5
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (RO1 AG037609)
- Japan Agency for Medical Research and Development
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- cholesterol homeostasis, Alzheimer's disease, lipid metabolism
- MeSH terms
- Alzheimer Disease, Animals, Biological Transport, Brain, Cholesterol, Gene Expression Regulation, Homeostasis, Humans, Signal Transduction, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Neurofibrillary Tangles, tau Proteins, Lipid Metabolism, Apolipoprotein E4
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