Table 2.
Studies of ABC transporters involved in Aβ transportation across the BBB
| Authors | Experiment models /measures | Conclusion |
|---|---|---|
| Sugiyama et al., 2003 | Mdr1a/Mdr1b and Mrp1 knockout mice; Mrp2-deficient mutant rats | Mrp1, but not Mrp2, was involved in the excretion of E217betaG at the BBB. |
| Nies et al., 2004 | Rapidly frozen perilesional samples of several regions of adult human brain | The proteins MRP1, MRP4, and MRP5 were clearly localized on the luminal side of brain capillary endothelial cells. |
| Koldamova et al., 2005 | APP23 mice | Lack of ABCA1 considerably decreased brain ApoE level and increased amyloid deposition. |
| Tachikawa et al., 2005 | Using in situ hybridization for the mouse brain | ABCG2 showed its preferential expression on the luminal membrane of brain capillaries. |
| Wahrle et al., 2005 | PDAPP Abca1–/– mice | PDAPP Abca1–/– mice produced poorly lipidated apoE and apoE deposits co-localized with amyloid plaques. |
| Akanuma et al., 2008 | ABCA1-expressing HEK293 cells; ABCA1-deficient mice | ABCA1 did not directly transport hA beta (1–40). |
| Xiong et al., 2009 | Tg-SwDI and 3XTg mice | ABCG2 was significantly upregulated in the brains of AD/CAA mice. |
| Hartz et al., 2010 | Human amyloid precursor protein (hAPP)-overexpressing mice; Tg2576 strain | Brain capillary P-glycoprotein expression and transport activity were substantially reduced in hAPP-overexpressing mice. |
| Krohn et al., 2011 | ABCB1- and ABCC1-deficient APP/PS1mice | Deficiency of ABCC1 substantially increased cerebral Aβ levels |
| Terwel et al., 2011 | APP23 mice | Increased association of microglia and Aβ plaques was dependent on the presence of LXRα and was accompanied by increased ApoE lipidation. |
| Abuznait et al., 2012 | LS-180 cells treatment with drugs known to induce P-gp expression | The investigated drugs were able to improve the efflux of Aβ1–40 from the cells via P-gp up-regulation. |
| Do et al., 2012 | HEK293 cells transfected with human ABCG2 or mouse abcg4; Abcb1/Abcg2-deficient mice; Abcb1-deficient mice | Abcg2 was involved in the transport of Aβ at the mouse BBB and the expression of Abcg2 was increased in neurons. |
| Zhao et al., 2015 | Post-mortem paraffin embedded human frontal cortex and hippocampus samples; APPsw/0; Picalm+/– mice ; primary human brain endothelial cells | Diminished Aβ clearance and accelerated pathology were observed in APPsw/0 Picalm+/– mice; PICALM/clathrin-dependent endocytosis of Aβ-LRP1 complex was observed on endothelial cells. |
| Storck et al., 2018 | With immunoprecipitation experiments, coimmunostainings and dual inhibition of ABCB1/P-gp and LRP1 | Late-onset AD risk factor PICALM was associated with both ABCB1/P-gp and LRP1 representing a functional link and guiding both proteins through the brain endothelium. |
| Chai et al., 2020 | Brain capillaries from P-gp-knockout mice | P-gp mediated Aβ export from the BBB endothelium. |
Aβ: Amyloid-beta; ABC: ATP-binding cassette; AD: Alzheimer’s disease; ApoE: apolipoprotein E; APP: amyloid precursor protein; BBB: blood-brain barrier; CAA: cerebral amyloid angiopathy; LRP1: low density lipoprotein receptor (LDLR)-related protein 1; LXR: Liver X Receptor; Mrp1: multidrug resistance associated protein 1; P-gp: P-glycoprotein; PICALM: phosphatidylinositol binding clathrin assembly protein.