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A Role for P-Glycoprotein in Clearance of Alzheimer Amyloid β -Peptide from the Brain

[ Vol. 13 , Issue. 6 ]

Author(s):

Wei Wang, Angela M. Bodles-Brakhop and Steven W. Barger   Pages 615 - 620 ( 6 )

Abstract:


Most data indicates that Alzheimer’s disease involves an accumulation of amyloid β - peptide (Aβ) in the CNS and that sporadic cases arise from a deficiency in Aβ clearance. Considerable attention has been given to mechanisms by which Aβ might be transported between the brain and blood, and evidence suggests that p-glycoprotein, also known as the multi-drug resistance (MDR) protein (product of the ABCB1 gene), plays a role in Aβ transport across the blood-brain barrier (BBB). We tested this possibility through two approaches: First, wild-type and MDR1A-knockout mice were compared after intravenous injection of [125I]-labeled Aβ; after 60 min, homogenates of brain parenchyma were subjected to γ-counting of TCA-precipitable material, and histological sections of brain were subjected to autoradiography. Second, MDR1Aknockout mice were crossed with Tg2576 APP transgenic mice, a line that routinely accumulates Aβ in the brain; SDS and formic acid extracts of brain homogenates were assessed for Aβ levels by ELISA. Each of these approaches yielded data indicating that Aβ accumulates to a greater degree in mice lacking MDR1A. These findings confirm other reports linking p-glycoprotein to Aβ clearance across the BBB and have important implications for Alzheimer’s disease genetics, pharmacology, and epidemiology.

Keywords:

Alzheimer’s disease, amyloid β -peptide, blood-brain barrier, blood-cerebrospinal fluid barrier, MDR1, p-glycoprotein, transport.

Affiliation:

Reynolds Institute on Aging, #807, 629 Jack Stephens Drive, Little Rock AR 72205, USA.



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