Table 2. BBB breakdown in APOE... | Rockefeller University Press

Table 2.

BBB breakdown in APOE transgenic models

Mouse line	Findings	Age	Region	Reference
Apoe^−/−	BBB leakage of Evans blue, IgG perivascular deposits	2 and 3 mo	Hippocampus, cerebellum, spinal cord	Fullerton et al., 2001
	BBB leakage of Evans blue, BBB leakage of peroxidase	1.5 and 2 mo	Cortex	Methia et al., 2001
	IgG perivascular deposits, brain leakage of exogenous tracer (sodium fluorescein)	11 mo	Hippocampus, cerebellum	Mulder et al., 2001
	BBB leakage of Evans blue	3 and 4 mo	Cortex, cerebellum	Hafezi-Moghadam et al., 2007
	BBB leakage of Evans blue	6 mo	Cortex, cerebellum	Nishitsuji et al., 2011
	BBB extravasation of exogenous tracers (Dextran and Cadaverine), fibrin perivascular deposits, thrombin perivascular deposits, IgG perivascular deposits, hemosiderin deposits, loss of CD13⁺/PDGFRβ⁺ pericytes, loss of BBB tight junctions,^{^a},^{^b} increased MMP-9 vascular expression	2 wk and 4, 6, 8, 9, and 18 mo	Cortex, hippocampus	Bell et al., 2012
	Fibrin perivascular deposits, loss of PDGFRβ⁺ pericytes, basement membrane degeneration	9 mo	Cortex	Soto et al., 2015
	BBB leakage of extracted immunoglobulin fractions directed against NMDAR, behavior alterations after injection of immunoglobulin fractions directed against NMDAR	3 and 4 mo	Cortex, hippocampus, cerebellum, brainstem, spinal cord	Hammer et al., 2014; Castillo-Gomez et al., 2016
	IgG perivascular deposits, increased BBB permeability to Gadolinium contrast agent	10 and 11 mo	Periventricular zone, fornix fimbria (hippocampus)	Di Cataldo et al., 2016
TR-APOE4 and GFAP-APOE4	BBB extravasation of exogenous tracers (Dextran and Cadaverine), fibrin perivascular deposits, thrombin perivascular deposits, IgG perivascular deposits, microhemorrhages (hemosiderin deposits),^{^c} loss of CD13⁺/PDGFRβ⁺ pericytes, loss of BBB tight junctions,^{^a},^{^b} increased MMP-9 vascular expression	2 wk and 4, 6, 8, 9, and 18 mo	Cortex, hippocampus	Bell et al., 2012
TR-APOE4	Basement membrane degeneration, loss of GLUT1 endothelial expression, increased RAGE endothelial expression	12 mo	Cortex, hippocampus	Alata et al., 2015
	Microhemorrhages (hemosiderin deposits)^{^d}	6 and 7 mo	Cortex	Cacciottolo et al., 2016
APOE4 knock-in	BBB leakage of Evans blue	6 mo	Cortex, cerebellum	Nishitsuji et al., 2011

Mouse line	Findings	Age	Region	Reference
Apoe^−/−	BBB leakage of Evans blue, IgG perivascular deposits	2 and 3 mo	Hippocampus, cerebellum, spinal cord	Fullerton et al., 2001
	BBB leakage of Evans blue, BBB leakage of peroxidase	1.5 and 2 mo	Cortex	Methia et al., 2001
	IgG perivascular deposits, brain leakage of exogenous tracer (sodium fluorescein)	11 mo	Hippocampus, cerebellum	Mulder et al., 2001
	BBB leakage of Evans blue	3 and 4 mo	Cortex, cerebellum	Hafezi-Moghadam et al., 2007
	BBB leakage of Evans blue	6 mo	Cortex, cerebellum	Nishitsuji et al., 2011
	BBB extravasation of exogenous tracers (Dextran and Cadaverine), fibrin perivascular deposits, thrombin perivascular deposits, IgG perivascular deposits, hemosiderin deposits, loss of CD13⁺/PDGFRβ⁺ pericytes, loss of BBB tight junctions,^a,^b increased MMP-9 vascular expression	2 wk and 4, 6, 8, 9, and 18 mo	Cortex, hippocampus	Bell et al., 2012
	Fibrin perivascular deposits, loss of PDGFRβ⁺ pericytes, basement membrane degeneration	9 mo	Cortex	Soto et al., 2015
	BBB leakage of extracted immunoglobulin fractions directed against NMDAR, behavior alterations after injection of immunoglobulin fractions directed against NMDAR	3 and 4 mo	Cortex, hippocampus, cerebellum, brainstem, spinal cord	Hammer et al., 2014; Castillo-Gomez et al., 2016
	IgG perivascular deposits, increased BBB permeability to Gadolinium contrast agent	10 and 11 mo	Periventricular zone, fornix fimbria (hippocampus)	Di Cataldo et al., 2016
TR-APOE4 and GFAP-APOE4	BBB extravasation of exogenous tracers (Dextran and Cadaverine), fibrin perivascular deposits, thrombin perivascular deposits, IgG perivascular deposits, microhemorrhages (hemosiderin deposits),^c loss of CD13⁺/PDGFRβ⁺ pericytes, loss of BBB tight junctions,^a,^b increased MMP-9 vascular expression	2 wk and 4, 6, 8, 9, and 18 mo	Cortex, hippocampus	Bell et al., 2012
TR-APOE4	Basement membrane degeneration, loss of GLUT1 endothelial expression, increased RAGE endothelial expression	12 mo	Cortex, hippocampus	Alata et al., 2015
	Microhemorrhages (hemosiderin deposits)^d	6 and 7 mo	Cortex	Cacciottolo et al., 2016
APOE4 knock-in	BBB leakage of Evans blue	6 mo	Cortex, cerebellum	Nishitsuji et al., 2011

APOE, apolipoprotein E; GFAP, glial fibrillary acidic protein; GLUT1, glucose transporter 1; IgG, immunoglobulin G; MMP-9, matrix metalloproteinase-9; NMDAR, N-methyl-d-aspartate receptor; PDGFRβ, platelet derived growth factor β; RAGE, receptor for advanced glycation end products; TR, targeted replacement.

Loss of BBB tight junctions as shown by high-resolution confocal microscopy analysis.

Loss of BBB tight junctions as shown by immunoblotting of isolated brain capillaries.

Microhemorrhages (hemosiderin deposits) at the capillary level.

Microhemorrhages (hemosiderin deposits) at the capillary and arteriolar level.

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