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

Author(s): Wei Wang, Angela M. Bodles-Brakhop, Steven W. Barger.

Journal Name: Current Alzheimer Research

Volume 13 , Issue 6 , 2016

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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.

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Article Details

VOLUME: 13
ISSUE: 6
Year: 2016
Page: [615 - 620]
Pages: 6
DOI: 10.2174/1567205013666160314151012
Price: $58

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