Alteration in the Function and Expression of SLC and ABC Transporters in the Neurovascular Unit in Alzheimer’s Disease and the Clinical Significance

Jia Yongming, Wang Na, Zhang Yingbo, Xue Di, Lou Haoming, Liu Xuewei

Table 1 An overview of the SLC and ABC transporters in the brain, with the proposed relevance to AD pathology.

Transporter Location Function References EAAT1/2 Expressed in astrocytes Regulate glutamate homeostasis and affect excitotoxic neuronal damage in AD [40] GLUT1 Expressed in endothelial cell, neurons, astrocytes and microglia Regulate glucose homeostasis in the brain Accelerate BBB breakdown, following secondary neurodegeneration caused by Aβ [52] [60] ABCB1 Expressed in endothelial cells, pericytes, astrocytes, the choroid plexus and neurons Transport of endoxenobiotics across the encephalon Involved in the clearance of Aβ from the brain into blood ABCB1 at the BBB declines during normal aging [83] [85] [90] ABCG2 Highly expressed in BBB endothelial cells Mediates the cellular efflux of Aβ in HEK293 cells [103] ABCG4 Expressed in brain capillary endothelial cells, glial cells and neurons Mediates the efflux of cholesterol to form apoE-containing lipoprotein Suppresses ABCG1 and ABCG4 function and increases Aβ secretion Mediates the cellular efflux of Aβ in HEK293 cells stably transfected with mouse abcg4 [109, 110] [111] [103] ABCA1 Widely expressed in brain tissues Stimulates the efflux of cholesterol and phospholipid to ApoE Increased ABCA1 levels induced by LXR ligands can increase the secreted Aβ concentration Decreases the influx of Aβ across the BBB Regulates the levels of ApoE and ApoE lipidation ABCA1 rs2422493 (C-477T) polymorphism are associated with increasing AD risk [113] [118] [117] [119] [126] ABCA7 Expressed in microglia, neurons, and brain endothelial cells Mediates the transfer of phospholipids and cholesterol across cell membranes Inhibits Aβ secretion without affecting the activities of α- and β-secretases Plays roles in APP processing, leading to enhanced Aβ secretion Phagocytic Aβ clearance in microglia is reduced in Abca7-/- mice ABCA7 SNPs are relate to the occurrence of AD [132] [132] [133] [136] [145] ABCC1 Localized in brain endothelial cells, astrocytes and pericytes Lack of ABCC1 could increase Aβ40 and Aβ42 levels compared to those in ABCC1-positive controls [153]