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Cited by 353Alzheimer's disease research and treatmentsFatty Acid Research and HealthLipid metabolism and biosynthesis

Involvement of Lipids in Alzheimer’s Disease Pathology and Potential Therapies

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Chew, Hannah, Solomon, Victoria A., Fonteh, Alfred N.·2020·Frontiers in Physiology
DOI 10.3389/fphys.2020.00598PMC PMC7296164
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Abstract

Lipids constitute the bulk of the dry mass of the brain and have been associated with healthy function as well as the most common pathological conditions of the brain. Demographic factors, genetics, and lifestyles are the major factors that influence lipid metabolism and are also the key components of lipid disruption in Alzheimer's disease (AD). Additionally, the most common genetic risk factor of AD, APOE ϵ4 genotype, is involved in lipid transport and metabolism. We propose that lipids are at the center of Alzheimer's disease pathology based on their involvement in the blood-brain barrier function, amyloid precursor protein (APP) processing, myelination, membrane remodeling, receptor signaling, inflammation, oxidation, and energy balance. Under healthy conditions, lipid homeostasis bestows a balanced cellular environment that enables the proper functioning of brain cells. However, under pathological conditions, dyshomeostasis of brain lipid composition can result in disturbed BBB, abnormal processing of APP, dysfunction in endocytosis/exocytosis/autophagocytosis, altered myelination, disturbed signaling, unbalanced energy metabolism, and enhanced inflammation. These lipid disturbances may contribute to abnormalities in brain function that are the hallmark of AD. The wide variance of lipid disturbances associated with brain function suggest that AD pathology may present as a complex interaction between several metabolic pathways that are augmented by risk factors such as age, genetics, and lifestyles. Herewith, we examine factors that influence brain lipid composition, review the association of lipids with all known facets of AD pathology, and offer pointers for potential therapies that target lipid pathways.

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  • Imbalance of lipid homeostasis is associated with a high risk of Alzheimer's disease.

    “Research shows that the imbalance of lipid homeostasis is associated with a high risk of AD [105,106].”

    From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [106]

    The Concluding Remarks (page unavailable) state that lipid metabolism is dysregulated in AD, and the Figure 1 discussion links that dysregulation to AD pathology. These passages support an association, but they do not establish that lipid-homeostasis imbalance is associated with a high risk of developing AD. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Modification in fluidity of neuronal membranes is involved with brain aging and may play an important role in AD.

    “The modification in the fluidity of neuronal membranes is involved with brain aging and may play an important role in AD [106].”

    From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [106]

    The sections on demographic factors and amyloid precursor protein processing describe age-related changes in membrane lipids and lipid rafts that may contribute to AD pathology. They do not establish that a change in neuronal membrane fluidity itself is involved in brain aging or AD; “membrane fluidity” appears only in a reference title in the retrieved passages. Page numbers were not available in our copy. (LLM, conf=0.83)

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Authors
Chew, H., Solomon, V. A., & Fonteh, A. N.
Affiliations
  • Huntington Medical Research Institutes (US)
  • University of Southern California (US)
Corresponding author
Fonteh, Alfred N.
ORCID
Venue
Frontiers in Physiology
Publisher
Frontiers Media SA
Published
2020-06-09
Volume
11
Pages
598-598
ISSN
1664-042X (ISSN-L)
DOI
10.3389/fphys.2020.00598
PMC
PMC7296164
OpenAlex
W3034639723
Cited by
353
References
42
Citations by year
2026: 43 · 2025: 69 · 2024: 59 · 2023: 72 · 2022: 51 · 2021: 47 · 2020: 10 · 2019: 2
FWCI
5.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Physiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • L. K. Whittier Foundation
  • National Institute on Aging (R01AG055770, R01AG054434)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
Alzheimer's disease, brain lipids, lipid metabolism, APOE ε4, blood-brain barrier, APP processing, myelination, membrane remodeling, neuroinflammation, oxidative stress, brain energy metabolism, lipid homeostasis

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