The Role of Lipids and Membranes in the Pathogenesis of Alzheimer's Disease: A Comprehensive View
Abstract
Lipids participate in Amyloid Precursor Protein (APP) trafficking and processing - important factors in the initiation of Alzheimer’s disease (AD) pathogenesis and influence the formation of neurotoxic β-amyloid (Aβ) peptides. An important risk factor, the presence of ApoE4 protein in AD brain cells binds the lipids to AD. In addition, lipid signaling pathways have a crucial role in the cellular homeostasis and depend on specific protein-lipid interactions. The current review focuses on pathological alterations of membrane lipids (cholesterol, glycerophospholipids, sphingolipids) and lipid metabolism in AD and provides insight in the current understanding of biological membranes, their lipid structures and functions, as well as their role as potential therapeutic targets. Novel methods for studying the membrane structure and lipid composition will be reviewed in a broad sense whereas the use of lipid biomarkers for early diagnosis of AD will be shortly summarized. Interactions of Aβ peptides with the cell membrane and different subcellular organelles are reviewed. Next, the details of the most important lipid signaling pathways, including the role of the plasma membrane as stress sensor and its therapeutic applications are given. 4-hydroxy-2-nonenal may play a special role in the initiation of the pathogenesis of AD and thus the “calpain-cathepsin hypothesis” of AD is highlighted. Finally, the most important lipid dietary factors and their possible use and efficacy in the prevention of AD are discussed.
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Genetic association studies of late-onset AD identified risk factors such as APOE that modulate Aβ processing, trafficking, and clearance.
“Subsequent genetic association studies of LOAD bolstered this framework, identifying risk factors such as APOE that modulate Aβ processing, trafficking, and clearance [19, 20, 30].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [30]
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- Authors
- Penke, B., Paragi, G., Gera, J., Berkecz, R., Kovács, Z., Crul, T., & VÍgh, L.
- Affiliations
- University of Szeged (HU)
- Eötvös Loránd University (HU)
- HUN-REN Szegedi Biológiai Kutatóközpont (HU)
- Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Temesvari krt. 62, H-6726 Szeged, Hungary
- Corresponding author
- Penke, Botond
- Venue
- Current Alzheimer Research
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2018-10-29
- Volume
- 15
- Issue
- 13
- Pages
- 1191-1212
- ISSN
- 1567-2050 (ISSN-L)
- OpenAlex
- W2891525057
- Cited by
- 55
- References
- 0
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 12 · 2019: 11
- FWCI
- 5.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Alzheimer Research (publishedVersion)
- PubMed (publishedVersion)
- SZTE Publicatio Repozitórium (University of Szeged) (acceptedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease pathogenesis, membrane lipids, APP processing, amyloid-beta, APOE ε4, cholesterol, glycerophospholipids, sphingolipids, lipid metabolism, membrane structure, lipid biomarkers, early diagnosis, 4-hydroxynonenal, dietary fat, Alzheimer's disease prevention
- MeSH terms
- Alzheimer Disease, Animals, Cell Membrane, Humans, Lipids, Lipid Metabolism
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