| 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.