ApoE4 Astrocytes Secrete Basement Membranes Rich in Fibronectin and Poor in Laminin Compared to ApoE3 Astrocytes
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The accumulation of amyloid-β (Aβ) in the walls of capillaries and arteries as cerebral amyloid angiopathy (CAA) is part of the small vessel disease spectrum, related to a failure of elimination of Aβ from the brain. Aβ is eliminated along basement membranes in walls of cerebral capillaries and arteries (Intramural Peri-Arterial Drainage—IPAD), a pathway that fails with age and ApolipoproteinEε4 (ApoE4) genotype. IPAD is along basement membranes formed by capillary endothelial cells and surrounding astrocytes. Here, we examine (1) the composition of basement membranes synthesised by ApoE4 astrocytes; (2) structural differences between ApoE4 and ApoE3 astrocytes, and (3) how flow of Aβ affects Apo3/4 astrocytes. Using cultured astrocytes expressing ApoE3 or ApoE4, immunofluorescence, confocal, correlative light and electron microscopy (CLEM), and a millifluidic flow system, we show that ApoE4 astrocytes synthesise more fibronectin, possess smaller processes, and become rarefied when Aβ flows over them, as compared to ApoE3 astrocytes. Our results suggest that basement membranes synthesised by ApoE4 astrocytes favour the aggregation of Aβ, its reduced clearance via IPAD, thus promoting cerebral amyloid angiopathy.
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ApoE4-expressing astrocytes show morphological alterations, with fewer and shorter processes and elongated cell bodies.
“ApoE4-expressing astrocytes also show morphological alterations, with fewer and shorter processes and elongated cell bodies [55]”
From Apoe4 and Alzheimer’s Disease Pathogenesis—Mitochondrial Deregulation and Targeted Therapeutic Strategies (2023) · cites this paper as [55]
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Pires, M., & Rego, A. C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24010778 · Cited by 157 · see citing works
- Authors
- Keable, A., O’Neill, R., MacGregor Sharp, M., Gatherer, M., Yuen, H. M., Johnston, D. A., Weller, R. O., & Carare, R. O.
- Affiliations
- University of Southampton (GB)
- Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
- Corresponding author
- Carare, Roxana Octavia
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2020-06-19
- Volume
- 21
- Issue
- 12
- Pages
- 4371
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC7352194
- OpenAlex
- W3036691009
- Cited by
- 15
- References
- 9
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 2
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council (BBSRC 2014 Industrial CASE Studentship)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- APOE ε4, APOE3, astrocytes, basement membrane, fibronectin, laminin, amyloid-beta, cerebral amyloid angiopathy, amyloid-beta clearance, amyloid-beta aggregation, astrocyte morphology, cerebral small vessel disease
- MeSH terms
- Apolipoproteins E, Astrocytes, Basement Membrane, Cells, Cultured, Fibronectins, Fluorescent Antibody Technique, Humans, Laminin, Microscopy, Electron, Amyloid beta-Peptides, Alternative Splicing, Microscopy, Confocal, Apolipoprotein E3, Apolipoprotein E4
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