Quantitation of ATP-binding cassette subfamily-A transporter gene expression in primary human brain cells

Abstract

Five ATP-binding cassette (ABC) subfamily-A transporters (ABCA1, ABCA2, ABCA3, ABCA7 and ABCA8) are expressed in the brain. These transporters may regulate brain lipid transport; however, their relative expression level in isolated human brain cells is unknown. We developed real-time polymerase chain reaction assays to quantify the expression of these genes in human neurons, astrocytes, oligodendrocytes, microglia and cell lines. Neurons expressed predominantly ABCA1 and ABCA3; astrocytes ABCA1, ABCA2 and ABCA3; microglia ABCA1 and oligodendrocytes ABCA2 and ABCA3. Although ABCA7 and ABCA8 expression was relatively low in all cells, the highest expression occurred in microglia and neurons, respectively. ABCA gene expression in the NTERA-2 and MO3.13 cell lines closely resembled the ABCA expression pattern of primary neurons and oligodendrocytes, respectively.

Astrocytic transporters in Alzheimer's disease

“…ABCA transporters (ABCA1-13) have been shown to regulate lipid transport and gene expression data highlights that human astrocytes express ABCA1-3 at the mRNA level (220). There is however contrasting evidence at the protein level (221,222).…”

“…For example, ABCA7 has been strongly implicated in APP processing, Aβ generation and the onset of dementia (224,225). However, the individual cellular role(s) of ABCA7 remains unresolved, and this is key given its widespread distribution (220,225). This shortfall in our understanding currently limits a critical appraisal of the role these astrocytic transporters may play in revealing a novel strategy to better manage AD pathology.…”

ABC transporters, neural stem cells and neurogenesis – a different perspective

“…A recent real-time reverse transcription-polymerase chain reaction (RT-PCR) assay has been used to investigate the specific expression pattern of the ABC subfamily-A transporters in the brain and has shown that neurons express predominantly ABCA1 and ABCA3; astrocytes express ABCA1, ABCA2 and ABCA3; microglia express ABCA1 and oligodendrocytes express ABCA2 and ABCA3 [105]. With its expression in liver and brain, ABCB1 -the prototype of the B subclass of transporters -and ABCA1 regulate the high-density lipoprotein levels in the plasma and cholesterol contents of several cell types in these organs [106][107][108][109][110][111][112][113][114].…”

ABCA7 and risk of dementia and vascular disease in the Danish population

“…ABCA7 is highly expressed in brain tissue,9, 21, 22 most abundant in microglia and oligodendrocytes 7, 23. Previous studies comparing ABCA7 knock‐out mice with wild‐type mice or J20 amyloidogenic mice demonstrate that ABCA7 is involved in clearance of amyloid‐ β in the brain through phagocytosis 12, 24.…”