Blood-Brain-Barrier Models for the Investigation of Transporter- and Receptor-Mediated Amyloid-β Clearance in Alzheimer's Disease

Alzheimer's disease (AD) is the most common form of dementia in the elderly with more than 26 million people worldwide living with the disease. Besides the main neuropathological hallmarks of AD, provoked by the accumulation of amyloid-β (Aβ) and tau hyperphosphorylation, other cells and cellular systems such as microglia and the neurovascular unit establishing the blood-brain-barrier (BBB) have been implicated to play a role in AD etiopathology. Insulating the brain from the blood stream, the BBB facilitates supply and disposal of nutrients and metabolites by the expression of transporters and transcytotic receptors at the polarized endothelial cell (EC) surface. Recently, several proteins involved in Aβ transport across the BBB have been identified in in vitro and in vivo studies. In this review, we summarize recent evidence of receptor- and transporter-mediated Aβ clearance across the BBB. Furthermore, we discuss the models used to identify and characterize Aβ transport across the BBB in regard to barrier properties and their suitability for experimental investigation of Aβ clearance mechanisms at an EC barrier.