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Review
. 2014 Sep 19;6:251.
doi: 10.3389/fnagi.2014.00251. eCollection 2014.

The Cerebrovascular Basement Membrane: Role in the Clearance of β-Amyloid and Cerebral Amyloid Angiopathy

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Free PMC article
Review

The Cerebrovascular Basement Membrane: Role in the Clearance of β-Amyloid and Cerebral Amyloid Angiopathy

Alan W J Morris et al. Front Aging Neurosci. .
Free PMC article

Abstract

Cerebral amyloid angiopathy (CAA), the accumulation of β-amyloid (Aβ) peptides in the walls of cerebral blood vessels, is observed in the majority of Alzheimer's disease (AD) brains and is thought to be due to a failure of the aging brain to clear Aβ. Perivascular drainage of Aβ along cerebrovascular basement membranes (CVBMs) is one of the mechanisms by which Aβ is removed from the brain. CVBMs are specialized sheets of extracellular matrix that provide structural and functional support for cerebral blood vessels. Changes in CVBM composition and structure are observed in the aged and AD brain and may contribute to the development and progression of CAA. This review summarizes the properties of the CVBM, its role in mediating clearance of interstitial fluids and solutes from the brain, and evidence supporting a role for CVBM in the etiology of CAA.

Keywords: Alzheimer’s disease; basement membrane; cerebral amyloid angiopathy; perivascular drainage; β-amyloid.

Figures

Figure 1
Figure 1
Micrograph of cortical Wistar Kyoto rat capillary. The cerebrovascular basement membrane is the electron dense area between the six arrow heads. Lu, capillary lumen; Edc, endothelial cell; Ast, astrocyte end foot. TEM, 50,000×, scale bar, 500 nm.
Figure 2
Figure 2
Composition of the neurovascular unit. (A) Diagram of leptomeningeal artery. Viewed from the center: arterial lumen (red), endothelial cell (blue), cerebrovascular basement membrane (light green), vascular smooth muscle cells (orange) have a cerebrovascular basement membrane running between them and are penetrated by nerve fibres (yellow), pia mater (dark green), and astrocyte end foot (teal). (B) Micrograph of C57BL/6 mouse cortical artery. Lu, lumen; Edc, endothelial cell; Smc, vascular smooth muscle cell; CVBM, cerebrovascular basement membrane; Pm, pia mater; sub, subarachnoid space. TEM, 25,000×, scale bar, 1000 nm, image credit: Matthew M. Sharp. (C) Diagram of a cerebral capillary. Viewed from the center; capillary lumen (red), endothelial cell (blue), cerebrovascular basement membrane (light green), pericyte (purple), and astrocyte end foot (teal). (D) Micrograph of Wistar Kyoto rat cerebral capillary. Lu, lumen; Edc, endothelial cell; Pct, pericyte; CVBM, cerebrovascular basement membrane; Ast, astrocyte end foot. TEM, 50,000×; scale bar, 500 nm.
Figure 3
Figure 3
Micrographs showing the continuity between the extracellular matrix and the cerebrovascular basement membrane. (A,B) Wistar Kyoto rat cerebral capillary, TEM, 50,000× scale bar 500 nm. (C,D) Magnified insert highlighting continuity between the BM and extracellular matrix. The extracellular matrix is the electron dense area between the two arrow heads in (C,D). Ast, astrocyte end foot; CVBM, cerebrovascular basement membrane.
Figure 4
Figure 4
Diagram depicting the perivascular elimination of solutes along the cerebrovascular basement membrane of a cerebral capillary. The arterial pulsatile wave driving blood flow into the brain (red arrows) is followed by a refractory wave, which may drive the movement of interstitial fluid (ISF) out of the brain along the cerebrovascular basement membrane (green arrow). Conformational changes in cerebrovascular basement membranes during the refractory wave may provide a valve-like mechanism that promotes unidirectional flow of ISF. Viewed from the center: capillary lumen (red), endothelial cell layer (blue), cerebrovascular basement membrane (light green), pericyte (purple), and astrocyte end foot (teal) with a section removed beyond dotted line.

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