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Open AccessArticle

ApoE4 Astrocytes Secrete Basement Membranes Rich in Fibronectin and Poor in Laminin Compared to ApoE3 Astrocytes

Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(12), 4371; https://doi.org/10.3390/ijms21124371
Received: 28 April 2020 / Revised: 12 June 2020 / Accepted: 16 June 2020 / Published: 19 June 2020
(This article belongs to the Special Issue Small Vessel Disease: A Whole Brain Disease)
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. View Full-Text
Keywords: apolipoprotein E4 astrocytes; basement membranes; correlative light and electron microscopy; millifluidics apolipoprotein E4 astrocytes; basement membranes; correlative light and electron microscopy; millifluidics
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MDPI and ACS Style

Keable, A.; O’Neill, R.; MacGregor Sharp, M.; Gatherer, M.; Yuen, H.M.; Johnston, D.A.; Weller, R.O.; Carare, R.O. ApoE4 Astrocytes Secrete Basement Membranes Rich in Fibronectin and Poor in Laminin Compared to ApoE3 Astrocytes. Int. J. Mol. Sci. 2020, 21, 4371. https://doi.org/10.3390/ijms21124371

AMA Style

Keable A, O’Neill R, MacGregor Sharp M, Gatherer M, Yuen HM, Johnston DA, Weller RO, Carare RO. ApoE4 Astrocytes Secrete Basement Membranes Rich in Fibronectin and Poor in Laminin Compared to ApoE3 Astrocytes. International Journal of Molecular Sciences. 2020; 21(12):4371. https://doi.org/10.3390/ijms21124371

Chicago/Turabian Style

Keable, Abby; O’Neill, Ronan; MacGregor Sharp, Matthew; Gatherer, Maureen; Yuen, Ho M.; Johnston, David A.; Weller, Roy O.; Carare, Roxana O. 2020. "ApoE4 Astrocytes Secrete Basement Membranes Rich in Fibronectin and Poor in Laminin Compared to ApoE3 Astrocytes" Int. J. Mol. Sci. 21, no. 12: 4371. https://doi.org/10.3390/ijms21124371

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