Apolipoprotein E in lipid metabolism and neurodegenerative disease
Open accessAbstract
Dysregulation of lipid metabolism has emerged as a central component of many neurodegenerative diseases. Variants of the lipid transport protein, apolipoprotein E (APOE), modulate risk and resilience in several neurodegenerative diseases including late-onset Alzheimer's disease (LOAD). Allelic variants of the gene, APOE, alter the lipid metabolism of cells and tissues and have been broadly associated with several other cellular and systemic phenotypes. Targeting APOE-associated metabolic pathways may offer opportunities to alter disease-related phenotypes and consequently, attenuate disease risk and impart resilience to multiple neurodegenerative diseases. We review the molecular, cellular, and tissue-level alterations to lipid metabolism that arise from different APOE isoforms. These changes in lipid metabolism could help to elucidate disease mechanisms and tune neurodegenerative disease risk and resilience.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
APOE is a protein canonically secreted to the extracellular space where it functions as a lipid transporter.
“APOE is a protein canonically secreted to the extracellular space where it functions as a lipid transporter95.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [95]
APOE genetic variation is a major risk factor for late-onset Alzheimer's disease, with the ε2 allele lowering risk, ε3 neutral, and ε4 increasing risk.
“Genetic variation in apolipoprotein E (APOE) is a major risk factor for late onset AD (LOAD) where the ε2 allele lowers risk, the ε3 allele affords neutral risk, and the ε4 allele increases risk 2 .”
From APOE4-drives brain bioenergetic shifts independent of Alzheimer’s disease pathology (2026) · cites this paper as [2]
APOE is the strongest genetic modulator of late-onset Alzheimer's disease and exists in common variants that confer decreased, neutral, or increased risk.
“Among these, coding variants of the APOE gene stand out as the strongest genetic risk and resilience factors for late-onset AD. The APOE3 allele is the most common and regarded as neutral with respect to AD risk, while single amino acid coding variants result in the APOE4 allele (C112R), which increases AD risk, and the APOE2 allele (R158C), which decreases AD risk12.”
From APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics (2026) · cites this paper as [12]
Altered lipid droplet biology has been linked to both brain aging and neurodegenerative diseases.
“Altered lipid droplet biology has been linked to both brain aging and neurodegenerative diseases10–24.”
From APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics (2026) · cites this paper as [12]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 197 · Cited by 286
Research works printed but not linked: 10
- [27]27. Strittmatter WJ et al. (1993) Apolipoprotein E: High-avidity binding to β -amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Natl. Acad. Sci. U. S. A 90, 1977-1981 [PubMed: 8446617]
- [55]55. Brewer HBJ et al. (1983) NIH conference. Type III hyperlipoproteinemia: diagnosis, molecular defects, pathology, and treatment. Ann. Intern. Med 98, 623-640 [PubMed: 6846977]
- [69]69. Schmechel DE et al. (1993) Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc. Natl. Acad. Sci. U. S. A 90, 9649-9653 [PubMed: 8415756]
- [82]82. Koutsodendris N. et al. (2023) Neuronal APOE4 removal protects against tau-mediated gliosis, neurodegeneration and myelin deficits. Nat. Aging DOI: 10.1038/s43587-023-00368-3 · DOI · Paper page
- [87]87. Moulton MJ et al. (2021) Neuronal ROS-induced glial lipid droplet formation is altered by loss of Alzheimer's disease-associated genes. Proc. Natl. Acad. Sci. U. S. A 118
- [122]122. Novotny BC et al. (2022) Metabolomic and lipidomic signatures in autosomal dominant and late-onset Alzheimer's disease brains. Alzheimers. Dement DOI: 10.1002/alz.12800 · DOI
- [151]151. Conant R and Schauss AG (2004) Therapeutic applications of citicoline for stroke and cognitive dysfunction in the elderly: a review of the literature. Altern. Med. Rev 9, 17-31 [PubMed: 15005642]
- [155]155. Maurice D. (1987) A Review of Recent Clinical Trials in the Treatment of Alzheimer's Dementia. Psychiatr. Ann 17, 178-191
- [171]171. Egert S. et al. (2012) ApoE genotype: from geographic distribution to function and responsiveness to dietary factors. Proc. Nutr. Soc 71, 410-424 [PubMed: 22564824]
- [196]196. Lee S. et al. (2023) APOE4 drives transcriptional heterogeneity and maladaptive immunometabolic responses of astrocytes. bioRxiv DOI: 10.1101/2023.02.06.527204 · DOI
- Authors
- Yang, L. G., March, Z. M., Stephenson, R. A., & Narayan, P. S.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Narayan, Priyanka S.
- Venue
- Trends in Endocrinology & Metabolism
- Publisher
- Elsevier BV
- Published
- 2023-08
- Volume
- 34
- Issue
- 8
- Pages
- 430-445
- ISSN
- 1043-2760 (ISSN-L)
- PMC
- PMC10365028
- OpenAlex
- W4381887391
- Cited by
- 286
- References
- 197
- Citations by year
- 2026: 117 · 2025: 105 · 2024: 54 · 2023: 10
- FWCI
- 10.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Trends in Endocrinology and Metabolism (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke
- Chan Zuckerberg Initiative
- National Institute of Diabetes and Digestive and Kidney Diseases
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein E, APOE isoforms, lipid metabolism, neurodegenerative diseases, late-onset Alzheimer's disease, disease risk, disease resilience, lipid transport, metabolic pathways
- MeSH terms
- Alzheimer Disease, Apolipoproteins E, Humans, Phenotype, Neurodegenerative Diseases, Lipid Metabolism
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
