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Cited by 65Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchFatty Acid Research and Health

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New insights in lipid metabolism: potential therapeutic targets for the treatment of Alzheimer’s disease

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Cao, Yuan, Zhao, Lin-Wei, Chen, Zi-Xin, Li, Shao-Hua·2024·Frontiers in Neuroscience
DOI 10.3389/fnins.2024.1430465PMC PMC11422391
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Abstract

Alzheimer’s disease (AD) is increasingly recognized as being intertwined with the dysregulation of lipid metabolism. Lipids are a significant class of nutrients vital to all organisms, playing crucial roles in cellular structure, energy storage, and signaling. Alterations in the levels of various lipids in AD brains and dysregulation of lipid pathways and transportation have been implicated in AD pathogenesis. Clinically, evidence for a high-fat diet firmly links disrupted lipid metabolism to the pathogenesis and progression of AD, although contradictory findings warrant further exploration. In view of the significance of various lipids in brain physiology, the discovery of complex and diverse mechanisms that connect lipid metabolism with AD-related pathophysiology will bring new hope for patients with AD, underscoring the importance of lipid metabolism in AD pathophysiology, and promising targets for therapeutic intervention. Specifically, cholesterol, sphingolipids, and fatty acids have been shown to influence amyloid-beta (Aβ) accumulation and tau hyperphosphorylation, which are hallmarks of AD pathology. Recent studies have highlighted the potential therapeutic targets within lipid metabolism, such as enhancing apolipoprotein E lipidation, activating liver X receptors and retinoid X receptors, and modulating peroxisome proliferator-activated receptors. Ongoing clinical trials are investigating the efficacy of these strategies, including the use of ketogenic diets, statin therapy, and novel compounds like NE3107. The implications of these findings suggest that targeting lipid metabolism could offer new avenues for the treatment and management of AD. By concentrating on alterations in lipid metabolism within the central nervous system and their contribution to AD development, this review aims to shed light on novel research directions and treatment approaches for combating AD, offering hope for the development of more effective management strategies.

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Metadata

Authors
Cao, Y., Zhao, L.-W., Chen, Z.-X., & Li, S.-H.
Affiliations
Zhengzhou University (CN)
ORCID
Cao, Yuan
Venue
Frontiers in Neuroscience
Publisher
Frontiers Media SA
Published
2024-09-11
Volume
18
Pages
1430465-1430465
ISSN
1662-453X (ISSN-L)
DOI
10.3389/fnins.2024.1430465
PMC
PMC11422391
OpenAlex
W4402451898
Cited by
65
References
61
Citations by year
2026: 43 · 2025: 21 · 2024: 1
FWCI
2.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (82301501)
  • Henan Medical Science and Technique Foundation
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Keywords
Alzheimer's disease, lipid metabolism, therapeutic target, cholesterol, sphingolipids, fatty acids, amyloid-beta deposition, tau hyperphosphorylation, apolipoprotein E, liver X receptor, retinoid X receptor, peroxisome proliferator-activated receptors, ketogenic diet, statins, high-fat diet, lipid dysregulation

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