title: Beta-Amyloid Downregulates MDR1-P-Glycoprotein (Abcb1) Expression at the Blood-Brain Barrier in Mice.
abstract: Neurovascular dysfunction is an important component of Alzheimer's disease, leading to reduced clearance across the blood-brain barrier and accumulation of neurotoxic β-amyloid (Aβ) peptides in the brain. It has been shown that the ABC transport protein P-glycoprotein (P-gp, ABCB1) is involved in the export of Aβ from the brain into the blood. To determine whether Aβ influences the expression of key Aβ transporters, we studied the effects of 1-day subcutaneous Aβ1-40 and Aβ1-42 administration via Alzet mini-osmotic pumps on P-gp, BCRP, LRP1, and RAGE expression in the brain of 90-day-old male FVB mice. Our results demonstrate significantly reduced P-gp, LRP1, and RAGE mRNA expression in mice treated with Aβ1-42 compared to controls, while BCRP expression was not affected. The expression of the four proteins was unchanged in mice treated with Aβ1-40 or reverse-sequence peptides. These findings indicate that, in addition to the age-related decrease of P-gp expression, Aβ1-42 itself downregulates the expression of P-gp and other Aβ-transporters, which could exacerbate the intracerebral accumulation of Aβ and thereby accelerate neurodegeneration in Alzheimer's disease and cerebral β-amyloid angiopathy.
authors.affiliation: Department of Neuropathology, Institute of Pathology, University of Greifswald, 17487 Greifswald, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Brenn
authors.forename: Markus
authors.initials: M
authors.lastname: Grube
authors.forename: Michele
authors.initials: M
authors.lastname: Peters
authors.forename: Andrea
authors.initials: A
authors.lastname: Fischer
authors.forename: Gabriele
authors.initials: G
authors.lastname: Jedlitschky
authors.forename: Heyo K
authors.initials: HK
authors.lastname: Kroemer
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Warzok
authors.forename: Silke
authors.initials: S
authors.lastname: Vogelgesang