Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 3 complete abstracts (679 words), 9 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Protein components on the surface of lipoproteins. They form a layer surrounding the hydrophobic lipid core. There are several classes of apolipoproteins with each playing a different role in lipid transport and lipid metabolism. These proteins are synthesized mainly in the liver and the intestines.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Apolipoprotein.
Where it fits in the MeSH classification
- Broader topics
- Lipoproteins; Apoproteins
- Narrower topics
- Apolipoproteins A; Apolipoproteins B; Apolipoproteins C; Apolipoproteins D; Apolipoproteins E; Apolipoproteins L; Apolipoproteins M
Related concepts
- Lipoproteins
- Lipid Metabolism
- Liver
- Intestines
Research landscape
PubMed indexes 55,248 records tagged with the MeSH heading “Apolipoproteins” (counts retrieved 2026-10-31). 8,922 of them (16.1%) were published from 2020 onward, and the busiest period so far is through 1999 with 16,122 records.
Reviews account for 5,120 records (9.3%) and meta-analyses for 531. Randomized controlled trials number 1,979 (3.6%) as a share of all records on the topic.
Show the data
| Period | Records |
|---|---|
| through 1999 | 16,122 |
| 2000-2009 | 14,327 |
| 2010-2019 | 15,877 |
| 2020 onward | 8,922 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 5,120 | 9.3% |
| Meta-analyses | 531 | 1.0% |
| Randomized controlled trials | 1,979 | 3.6% |
Method: PubMed query "Apolipoproteins"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction | 2025 | Research article Design not recorded in structured metadata | 18 | cc by PMID 41103078 · DOI · PMC12758178 |
| Neuronal APOE4-induced early hippocampal network hyperexcitability in Alzheimer's disease pathogenesis | 2026 | Research article Design not recorded in structured metadata | 11 | cc by PMID 41933197 · DOI · PMC13099648 |
| ApoE4 Upregulates GSK-3β to Aggravate Alzheimer-Like Pathologies and Cognitive Impairment in Type 2 Diabetic Mice | 2025 | Research article Design not recorded in structured metadata | 9 | cc by PMID 40905109 · DOI · PMC12409304 |
Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction [1]
Abstract reading summary — source excerpts
- Opening excerpt
- APOE4 is the primary risk factor for Alzheimer disease (AD).
- Closing excerpt
- Abbreviation: Aβ-β-amyloid; AD-Alzheimer disease; APMS-affinity purification mass spectrometry; APOE-apolipoprotein E; APP-amyloid beta precursor protein; BafA1-bafilomycin A1; CMA-chaperone-mediated autophagy; COP-coatomer; ER-endoplasmic reticulum; ERAD-endoplasmic reticulum-associated degradation; ERGIC-endoplasmic reticulum-Golgi intermediate compartment; FCCP-carbonyl cyanide p-trifluoromethoxyphenylhydrazone; GABA-gamma-aminobutyric acid; GFP-green fluorescent protein; GPI-glycerophosphoinositol; GPN-glycyl-L-phenylalanine 2-naphthylamide; HA-hemagglutinin protein tag; iPSC-induced pluripotent stem cells; LAMP1-lysosomal associated membrane protein 1; LGALS3BP-galectin 3 binding protein; LysoIP-lysosomal immunoprecipitation; MAPT-microtubule associated protein tau; MR-CTSB-magic red cathepsin B; MS-mass spectrometry; NFT-neurofibrillary tangles; PCA-principal component analysis; PLA-proximity ligation assay; PSEN1-presenilin 1; PSEN2-presenilin 2; p-MAPT/Tau-phospho-MAPT/tau; ROS-reactive oxygen species; RT-qPCR-reverse transcriptase quantitative polymerase chain reaction; SEM-standard error of the mean; siRNA-short interfering RNA; SRCR-scavenger receptor cysteine-rich domain; TMED-transmembrane p24 trafficking protein; TMEM192-transmembrane protein 192.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (280 words)
APOE4 is the primary risk factor for Alzheimer disease (AD). Early AD pathological events first affect the neuronal endolysosomal system, which in turn causes neuronal protein aggregation and cell death. Despite the crucial influence of lysosomes upon AD pathophysiology, and that APOE4 localizes to lysosomes, the influence of APOE4 on lysosomal function remains unexplored. We find that expression of APOE4 in neuronal cell lines results in lysosomal alkalinization and impaired lysosomal function. To identify driving factors for these defects, we performed quantitative lysosomal proteome profiling. This revealed that APOE4 expression results in differential regulation of numerous lysosomal proteins, correlating with APOE allele status and disease severity in AD brains. In particular, APOE4 expression results in the depletion of lysosomal LGALS3BP and the accumulation of lysosomal TMED5. We additionally validated that these lysosomal protein changes can be targeted to modulate lysosomal function. Taken together, this work thereby reveals that APOE4 causes widespread lysosomal defects through remodeling the lysosomal proteome, with the lysosomal TMED5 accumulation and LGALS3BP depletion manifesting as lysosomal alkalinization in APOE4 neurons.Abbreviation: Aβ-β-amyloid; AD-Alzheimer disease; APMS-affinity purification mass spectrometry; APOE-apolipoprotein E; APP-amyloid beta precursor protein; BafA1-bafilomycin A1; CMA-chaperone-mediated autophagy; COP-coatomer; ER-endoplasmic reticulum; ERAD-endoplasmic reticulum-associated degradation; ERGIC-endoplasmic reticulum-Golgi intermediate compartment; FCCP-carbonyl cyanide p-trifluoromethoxyphenylhydrazone; GABA-gamma-aminobutyric acid; GFP-green fluorescent protein; GPI-glycerophosphoinositol; GPN-glycyl-L-phenylalanine 2-naphthylamide; HA-hemagglutinin protein tag; iPSC-induced pluripotent stem cells; LAMP1-lysosomal associated membrane protein 1; LGALS3BP-galectin 3 binding protein; LysoIP-lysosomal immunoprecipitation; MAPT-microtubule associated protein tau; MR-CTSB-magic red cathepsin B; MS-mass spectrometry; NFT-neurofibrillary tangles; PCA-principal component analysis; PLA-proximity ligation assay; PSEN1-presenilin 1; PSEN2-presenilin 2; p-MAPT/Tau-phospho-MAPT/tau; ROS-reactive oxygen species; RT-qPCR-reverse transcriptase quantitative polymerase chain reaction; SEM-standard error of the mean; siRNA-short interfering RNA; SRCR-scavenger receptor cysteine-rich domain; TMED-transmembrane p24 trafficking protein; TMEM192-transmembrane protein 192.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41103078 · DOI · PMC12758178
Neuronal APOE4-induced early hippocampal network hyperexcitability in Alzheimer's disease pathogenesis [2]
Abstract reading summary — source excerpts
- Opening excerpt
- The full impact of APOE4 (apolipoprotein E4), the strongest genetic risk factor for Alzheimer's disease (AD), on neuronal and network function remains unclear, particularly during early preclinical stages of disease.
- Closing excerpt
- Together, these findings define molecular and circuit mechanisms linking neuronal APOE4-induced early network impairment to AD pathogenesis with aging.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (146 words)
The full impact of APOE4 (apolipoprotein E4), the strongest genetic risk factor for Alzheimer's disease (AD), on neuronal and network function remains unclear, particularly during early preclinical stages of disease. Here we show that young APOE4 knockin (E4-KI) mice exhibit hippocampal region-specific network hyperexcitability that predicts later cognitive deficits. This early phenotype arises from cell-type-specific subpopulations of smaller, hyperexcitable neurons and is eliminated by selective removal of neuronal APOE4. With aging, E4-KI mice develop granule cell hyperexcitability, progressive inhibitory dysfunction and excitation-inhibition imbalance in the dentate gyrus. Single-nucleus RNA sequencing with multilevel gene filtering reveals age-dependent and cell-type-specific transcriptional changes and identifies candidate mediators of early neuronal hyperexcitability, including Nell2. Targeted CRISPR interference knockdown of Nell2 rescues abnormal excitability, implicating Nell2 as a contributor to APOE4-driven dysfunction. Together, these findings define molecular and circuit mechanisms linking neuronal APOE4-induced early network impairment to AD pathogenesis with aging.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41933197 · DOI · PMC13099648
ApoE4 Upregulates GSK-3β to Aggravate Alzheimer-Like Pathologies and Cognitive Impairment in Type 2 Diabetic Mice [3]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundThe apolipoprotein E (ApoE) ε4 allele and type 2 diabetes mellitus (T2DM) are independent risk factors for Alzheimer's disease (AD), the most prevalent neurodegenerative disorder in the elderly.
- Closing excerpt
- Furthermore, targeting GSK-3β may offer a promising therapeutic strategy to halt the progression from T2DM to AD, providing new insights into potential interventions for patients at risk.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (253 words)
BackgroundThe apolipoprotein E (ApoE) ε4 allele and type 2 diabetes mellitus (T2DM) are independent risk factors for Alzheimer's disease (AD), the most prevalent neurodegenerative disorder in the elderly. The T2DM patients carrying the ApoE ε4 allele exhibit heightened activation of platelet glycogen synthase kinase-3β (GSK-3β), a key downstream kinase in the insulin signaling pathway, along with more severe cognitive deficits. This observation suggests an intrinsic link between ApoE ε4, GSK-3β, and cognitive dysfunction. However, the precise mechanisms by which ApoE ε4 influences GSK-3β activity and exacerbates brain pathology and cognitive decline in T2DM patients remain poorly understood.MethodsTo investigate these mechanisms, we developed T2DM mouse models by generating humanized ApoE ε3/ε3 and ε4/ε4 knock-in mice. The mice were subjected to a high-fat diet combined with multiple low-dose intraperitoneal streptozotocin injections to induce T2DM. We then assessed GSK-3β expression, AD-like pathologies, and cognitive functions in these models.ResultsWe observed that GSK-3β activity was significantly upregulated in ApoE4 mice, accompanied by disruption of the insulin signaling pathway. Notably, ApoE4-T2DM mice exhibited exacerbated AD-related pathologies, including increased accumulation of hyperphosphorylated tau, neuroinflammation, and synaptic loss. These changes were correlated with more severe cognitive impairments compared with ApoE3-T2DM or ApoE4 mice. Furthermore, inhibition of GSK-3β activity using the selective inhibitor 9-ING-41 effectively ameliorated both AD-like pathologies and cognitive deficits in ApoE4-T2DM mice.ConclusionsOur findings suggest that ApoE4 exacerbates AD pathogenesis by activating GSK-3β. Furthermore, targeting GSK-3β may offer a promising therapeutic strategy to halt the progression from T2DM to AD, providing new insights into potential interventions for patients at risk.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40905109 · DOI · PMC12409304
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium [4]
- Research article Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis [5]
- Research article Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease: A Meta-analysis [6]
- Research article Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease [7]
- Research article A meta-analysis of genome-wide association studies identifies multiple longevity genes [8]
- Research article Effects of tree nuts on blood lipids, apolipoproteins, and blood pressure: systematic review, meta-analysis, and dose-response of 61 controlled intervention trials [9]
References
- Krogsaeter EK, McKetney J, Valiente-Banuet L, Marquez A, Willis A, Cakir Z, et al.. Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction. . 2025. PMID 41103078 · DOI · PMC12758178
- Tabuena DR, Jang SS, Grone B, Yip O, Aery Jones EA, Blumenfeld J, et al.. Neuronal APOE4-induced early hippocampal network hyperexcitability in Alzheimer's disease pathogenesis. . 2026. PMID 41933197 · DOI · PMC13099648
- Wang Y, Gao Y, Wang Y, Zhang F, Sun F, Wang X, et al.. ApoE4 Upregulates GSK-3β to Aggravate Alzheimer-Like Pathologies and Cognitive Impairment in Type 2 Diabetic Mice. . 2025. PMID 40905109 · DOI · PMC12409304
- Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al.. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997. PMID 9343467 · DOI
- Jansen WJ, Ossenkoppele R, Knol DL, Tijms BM, Scheltens P, Verhey FR, et al.. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA. 2015. PMID 25988462 · DOI · PMC4486209
- Neu SC, Pa J, Kukull W, Beekly D, Kuzma A, Gangadharan P, et al.. Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease: A Meta-analysis. JAMA Neurol. 2017. PMID 28846757 · DOI · PMC5759346
- Song Y, Stampfer MJ, Liu S. Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease. Ann Intern Med. 2004. PMID 15262670 · DOI
- Deelen J, Evans DS, Arking DE, Tesi N, Nygaard M, Liu X, et al.. A meta-analysis of genome-wide association studies identifies multiple longevity genes. Nat Commun. 2019. PMID 31413261 · DOI · PMC6694136
- Del Gobbo LC, Falk MC, Feldman R, Lewis K, Mozaffarian D. Effects of tree nuts on blood lipids, apolipoproteins, and blood pressure: systematic review, meta-analysis, and dose-response of 61 controlled intervention trials. Am J Clin Nutr. 2015. PMID 26561616 · DOI · PMC4658458
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.