Immunohistochemical analysis of transporters related to clearance of amyloid-β peptides through blood–cerebrospinal fluid barrier in human brain
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A large number of previous reports have focused on the transport of amyloid-β peptides through cerebral endothelial cells via the blood-brain barrier, while fewer reports have mentioned the transport through the choroid plexus epithelium via the blood-cerebrospinal fluid barrier. Concrete roles of these two pathways remain to be clarified. In this study, we immunohistochemically examined the expression of transporters/receptors that are supposed to be related to the clearance of amyloid-β peptides in the choroid plexus epithelium, the ventricular ependymal cells and the brain microvessels, using seven autopsied human brains. In the choroid plexus epithelium, immunoreactivity for low-density lipoprotein receptor (LDLR), LDLR-related protein 1 (LRP1), LRP2, formylpeptide receptor-like 1 (FPRL1), ATP-binding cassette (ABC) transporter-A1 (ABCA1), ABCC1 and ABCG4 was seen in 7 of 7 brains, while that for ABCB1, ABCG2, RAGE and CD36 was seen in 0-2 brains. In the ventricular ependymal cells, immunoreactivity for CD36, LDLR, LRP1, LRP2, FPRL1, ABCA1, ABCC1 and ABCG4 was seen in 6-7 brains, while that for ABCB1, ABCG2 and RAGE was seen in 0-1 brain. Immunoreactivity for insulin-degrading enzyme (IDE) was seen in three and four brains in the choroid plexus epithelium and the ventricular ependymal cells, respectively. In addition, immunoreactivity for LDLR, ABCB1 and ABCG2 was seen in over 40 % of the microvessels (all seven brains), and that for FPRL1, ABCA1, ABCC1 and RAGE was seen in over 5 % of the microvessels (4-6 brains), while that for CD36, IDE, LRP1, LRP2 and ABCG4 was seen in less than 5 % of the microvessels (0-2 brains). These findings may suggest that these multiple transporters/receptors and IDE expressed on the choroid plexus epithelium, ventricular ependymal cells and brain microvessels complementarily or cooperatively contribute to the clearance of amyloid-β peptides from the brain.
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The three RAGE forms bind various ligands with similar affinities, including AGEs and amyloid β peptide.
“The three RAGE forms bind various ligands with similar affinities, including multiple advanced glycation end-products (AGEs) and amyloid β peptide31–37.”
From Vascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice (2019) · cites this paper as [33]
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Chiba, Y., Sugiyama, Y., Nishi, N., Nonaka, W., Murakami, R., & Ueno, M. (2020) · Neuropathology · doi:10.1111/neup.12665 · Cited by 59 · see citing works
Self-citation
- Authors
- Matsumoto, K., Chiba, Y., Fujihara, R., Kubo, H., Sakamoto, H., & Ueno, M.
- Affiliations
- Kagawa University (JP)
- Corresponding author
- Ueno, Masaki
- Venue
- Histochemistry and Cell Biology
- Published
- 2015-10-08
- Volume
- 144
- Issue
- 6
- Pages
- 597-611
- ISSN
- 0948-6143 (ISSN-L)
- 1432-119X
- OpenAlex
- W1944592923
- Cited by
- 46
- References
- 107
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 6 · 2018: 3 · 2017: 7 · 2016: 5
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Histochemistry and Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (15K08425, 26430055)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- amyloid-beta clearance, blood-CSF barrier, choroid plexus epithelium, cerebral microvasculature, ABC transporters, LDL receptor, LRP1, megalin, FPRL1, ABCA1, ABCG4, P-glycoprotein, ABCG2, RAGE, CD36, insulin-degrading enzyme
- MeSH terms
- Blood-Brain Barrier, Brain, Cerebrospinal Fluid, Humans, Immunohistochemistry, Amyloid beta-Peptides, LDL-Receptor Related Proteins
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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.
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