Title:Blood-Brain Barrier ABC-transporter P-glycoprotein in Alzheimer's Disease: Still a Suspect?
Volume: 22
Issue: 38
Author(s): Danielle M.E. van Assema and Bart N.M. van Berckel
Affiliation:
Keywords:
P-glycoprotein / ABCB1, ABC transporters, Blood-brain barrier, Alzheimer's disease, amyloid.
Abstract: Alzheimer’s disease is a neurodegenerative disorder and the most common form
of dementia. One of the pathological hallmarks of the disease is amyloid deposition in the
brain. The major cause of amyloid deposition in sporadic Alzheimer’s disease is thought to
be decreased brain clearance of amyloid. There is compelling preclinical evidence that the
blood-brain barrier, a structure that maintains homeostasis in the central nervous system and
protects the brain from harmful substances, plays an important role in amyloid clearance.
Indeed, several dedicated transporter systems are present at the blood-brain barrier which
may have a role in brain amyloid clearance, such as P-glycoprotein (P-gp). In vitro experiments
and animal studies indicated increased amyloid deposition when P-gp was eliminated
by pharmacological blockade or by genetic modification. And as decreased P-gp expression
has been found in AD brains, P-gp became more and more a suspect. Using an imaging
technique called positron emission tomography, P-gp transporter function was found to be
decreased in Alzheimer’s disease patients compared to healthy controls, further establishing the important role of
P-gp in the pathogenesis of the disease. In this review, we summarize what is now known about P-gp in Alzheimer’s
disease pathology, as these transporters may provide a novel target for therapeutic strategies.
