BBA General Subjects

Results from LC/MS identifications and MALDI/imaging

Visualization of SV2A protein in primary neurons (14DIC): immunohistochemistry with anti-SV2A. SV2A protein is implicated in regulation of RRP and stimulated secretion in hippocampus

The blood-brain barrier (BBB) is highly restrictive in nature and helps maintain the privileged site status of the central nervous system (CNS). ATP-binding Cassette (ABC) transporters are major functional components of the BBB and significantly influence the BBB permeation of both endogenous and exogenous compounds. One of the key pathological characteristics of Alzheimer’s disease is production and aggregation of the amyloid beta (Aβ(1-42)) peptide within the brain. Whilst it has been demonstrated Aβ(1-42) reduces expression and activity of the ABCB1 efflux transporter in brain endothelial cells, no studies yet report the effects of Aβ(1-42) on the activity, or expression, of ABCC5 and ABCG2, which are other key efflux transporters expressed in the BBB. The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are widely expressed in BBB brain endothelial cells and are key regulators of ABC transporter expression. However, to date, no studies report the effects of Aβ(1-42) on PXR and CAR expression. The present study is the first to demonstrate that Aβ(1-42) is able to modify the expression and activity of multiple ABC efflux transporters, as well as modify expression of nuclear receptors which regulate transporter expression. These findings suggest that interaction of Aβ(1-42) with BBB endothelial cells down-regulates protective mechanisms within the BBB and may impact on penetration of compounds across the BBB.