Cited by 46Alzheimer's disease research and treatmentsCerebrospinal fluid and hydrocephalusBarrier Structure and Function Studies

Immunohistochemical analysis of transporters related to clearance of amyloid-β peptides through blood–cerebrospinal fluid barrier in human brain

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Matsumoto, Koichi, Chiba, Yoichi, Fujihara, Ryuji, Kubo, Hiroyuki, Sakamoto, Haruhiko, Ueno, Masaki·2015·Histochemistry and Cell Biology

Abstract

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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Crossref · 10.1007/s00418-015-1366-7

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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
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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