The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Isoform‐Specific Effects of Apolipoproteins E2, E3, and E4 on Cerebral Capillary Sequestration and Blood‐Brain Barrier Transport of Circulating Alzheimer's Amyloid β
Abstract
Abstract: Cerebral capillary sequestration and blood‐brain barrier (BBB) permeability to apolipoproteins E2 (apoE2), E3 (apoE3), and E4 (apoE4) and to their complexes with sAβ 1–40, a peptide homologous to the major form of soluble Alzheimer's amyloid β, were studied in perfused guinea pig brain. Cerebrovascular uptake of three apoE isoforms was low, their blood‐to‐brain transport undetectable, but uptake by the choroid plexus significant. Binding of all three isoforms to sAβ 1–40 in vitro was similar with a KD between 11.8 and 12.9 n M. Transport into brain parenchyma and sequestration by BBB and choroid plexus were negligible for sAβ 1–40‐apoE2 and sAβ 1–40‐apoE3, but significant for sAβ 1–40‐apoE4. After 10 min, 85% of sAβ 1–40‐apoE4 taken up at the BBB remained as intact complex, whereas free sAβ 1–40 was 51% degraded. Circulating apoE isoforms have contrasting effects on cerebral capillary uptake of and BBB permeability of sAβ. ApoE2 and apoE3 completely prevent cerebral capillary sequestration and blood‐to‐brain transport of sAβ 1–40. Conversely, apoE4, by entering brain microvessels and parenchyma as a stable complex with sAβ, reduces peptide degradation and may predispose to cerebrovascular and possibly enhance parenchymal amyloid formation under pathological conditions.
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In the citing paper
“A limited blood brain barrier permeability to circulating lipidpoor apoE2, apoE3, and apoE4 supports that apoE in blood and brain are regulated independently [72,107,108].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [107]
In the citing paper
“Further, previous work suggest a limited blood–brain barrier permeability to circulating lipid-poor apoE,62”
From Plasma levels of apolipoprotein E, APOE genotype, and all-cause and cause-specific mortality in 105 949 individuals from a white general population cohort (2019) · cites this paper as [62]
In the citing paper
“Finally, an apoE4-Aβ complex present in the periphery is sequestered into brain capillaries to a greater extent than Aβ bound to apoE2 or apoE3, demonstrating that apoE4-mediated blood to brain transport of Aβ may play a role in amyloid accumulation in the brain (Martel et al., 1997).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Martel et al., 1997
In the citing paper
“Previous studies from our laboratory and others have demonstrated a major role of the BBB in determining the concentrations of A b in the CNS by regulating transport of circulating A b (33, 39, 49-51, 62-66).”
From Clearance of Alzheimer’s amyloid-β1-40 peptide from brain by LDL receptor–related protein-1 at the blood-brain barrier (2000) · cites this paper as [51]
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The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
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Amyloid Beta: Structure, Biology and Structure-Based Therapeutic Development
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RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain
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Self-citation
Metadata
- Authors
- Martel, C. L., Mackic, J. B., Matsubara, E., Governale, S., Miguel, C., Miao, W., McComb, J. G., Frangione, B., Ghiso, J., & Zlokovic, B. V.
- Affiliations
- University of Southern California (US)
- NYU Langone Health (US)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1997-11
- Volume
- 69
- Issue
- 5
- Pages
- 1995-2004
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1974008457
- Cited by
- 149
- References
- 21
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 2 · 2014: 8 · 2013: 3 · 2012: 7
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS34467)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- apolipoprotein E isoforms, APOE2, APOE3, APOE ε4, blood-brain barrier permeability, amyloid beta degradation, amyloid deposition
- MeSH terms
- Amino Acid Sequence, Animals, Apolipoproteins E, Blood-Brain Barrier, Capillary Permeability, Cerebrovascular Circulation, Female, Guinea Pigs, Humans, Kinetics, Male, Molecular Sequence Data, Peptide Fragments, Perfusion, Recombinant Proteins, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2
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