A Role for P-Glycoprotein in Clearance of Alzheimer Amyloid ? -Peptide from the Brain
Open accessAbstract
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 [(125)I]-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.
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ABCB1 (P-glycoprotein) contributes to Alzheimer's Aβ toxin clearance from brain to blood.
“ABCB1 contributes to Alzheimer's A 𝛃 toxin clearance from brain-to-blood (115, 632).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [632]
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References 33 · Cited by 107
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- Authors
- Wang, W., M. Bodles-Brakhop, A., & W. Barger, S.
- ORCID
- Wang, Wei
- Venue
- Current Alzheimer Research
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2016-04-15
- Volume
- 13
- Issue
- 6
- Pages
- 615-620
- ISSN
- 1567-2050 (ISSN-L)
- PMC
- PMC5102249
- OpenAlex
- W2300070246
- Cited by
- 107
- References
- 33
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 13 · 2023: 14 · 2022: 9 · 2021: 14 · 2020: 12 · 2019: 9 · 2018: 9 · 2017: 7
- FWCI
- 6.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Alzheimer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P01AG012411)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- P-glycoprotein, mdr1a knockout mice, amyloid-beta clearance, blood-brain barrier, Alzheimer's disease, amyloid-beta transport, amyloid-beta deposition, Alzheimer's disease genetics
- MeSH terms
- Animals, Autoradiography, Blood-Brain Barrier, Brain, Enzyme-Linked Immunosorbent Assay, Humans, Mice, Transgenic, Peptide Fragments, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, ATP Binding Cassette Transporter, Subfamily B
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