ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2012
Apolipoprotein E does not cross the blood-cerebrospinal fluid barrier, as revealed by an improved technique for sampling CSF from mice.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 75 citations in OpenAlex.
- Beyond Lipidation: CSF APOE4 Protein Burden, Not HDL Subclass, Drives Tau Associations in APOE4 Alzheimer's Disease.Research square · 2026Article
- Article
- Reduction of APOE accounts for neurobehavioral deficits in fetal alcohol spectrum disorders.Molecular psychiatry · 2024Article
- Circulating apoE4 protein levels from dried blood spots predict cognitive function in a large population-based survey setting.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Readdressing the Localization of Apolipoprotein E (APOE) in Mitochondria-Associated Endoplasmic Reticulum (ER) Membranes (MAMs): An Investigation of the Hepatic Protein-Protein Interactions of APOE with the Mitochondrial Proteins Lon Protease (LONP1), Mitochondrial Import Receptor Subunit TOM40 (TOMM40) and Voltage-Dependent Anion-Selective Channel 1 (VDAC1).International journal of molecular sciences · 2024Article
- Insights into the roles of Apolipoprotein E in adipocyte biology and obesity.International journal of obesity (2005) · 2024Review
- Effect of Apolipoprotein E isoforms on the Abundance and Function of P-glycoprotein in Human Brain Microvascular Endothelial Cells.Pharmaceutical research · 2024Article
- Impact of arterial stiffness on cerebrovascular function: a review of evidence from humans and preclincal models.American journal of physiology. Heart and circulatory physiology · 2024Review
- Article
- Roles of peripheral lipoproteins and cholesteryl ester transfer protein in the vascular contributions to cognitive impairment and dementia.Molecular neurodegeneration · 2023Review
- The small HDL particle hypothesis of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Brain apolipoprotein E levels in mice challenged by a Western diet increase in an allele-dependent manner.Aging brain · 2023Article
- Article
- Apolipoprotein E imbalance in the cerebrospinal fluid of Alzheimer's disease patients.Alzheimer's research & therapy · 2022Article
- Review
- Labelfree mapping and profiling of altered lipid homeostasis in the rat hippocampus after traumatic stress: Role of oxidative homeostasis.Neurobiology of stress · 2022Article
- Functional diversity of apolipoprotein E: from subcellular localization to mitochondrial function.Cellular and molecular life sciences : CMLS · 2022Review
- TheFrontiers in aging neuroscience · 2022Article
- Mass spectrometry-based methods for robust measurement of Alzheimer's disease biomarkers in biological fluids.Journal of neurochemistry · 2021Review
- Identification of epigenome-wide DNA methylation differences between carriers of APOE ε4 and APOE ε2 alleles.Genome medicine · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Apolipoprotein E (apoE) is a 34-kDa glycoprotein that is important in lipoprotein metabolism both peripherally and centrally. Because it is primarily produced in the liver, apoE observed in the brain or cerebrospinal fluid (CSF) could have originated in the periphery; i.e., circulating apoE may cross the blood-brain barrier (BBB) and/or enter CSF and be taken up by brain cells. To determine whether this occurs, a second-generation adenovirus encoding human apoE3 was administered intravenously (iv) to C57BL/6J mice, and the detection of human apoE3 in the CSF was used as a surrogate measure of central availability of this protein utilizing an improved method for sampling CSF from mice. This improved technique collects mouse CSF samples with a 92% success rate and consistently yields relatively large volumes of CSF with a very low rate of blood contamination, as determined by molecular assessment of apolipoprotein B, a plasma-derived protein that is absent in the central nervous system. Through this improved method, we demonstrated that in mice receiving the administered apoE3 adenovirus, human apoE3 was expressed at high levels in the liver, leading to high levels of human apoE3 in mouse plasma. In contrast, human apoE3 levels in the CSF, as assessed by a sensitive ELISA, were essentially undetectable in human apoE3 adenovirus-treated mice, and comparable to levels in LacZ adenovirus-treated control mice. These data indicate that apoE in the CSF cannot be derived from the plasma pool and, therefore, must be synthesized locally in the brain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.