Evidence map›Paper›PMID 30041013›Full record

ArticleBrain, behavior, and immunity2018

The concerted amyloid-beta clearance of LRP1 and ABCB1/P-gp across the blood-brain barrier is linked by PICALM.

Steffen E Storck, Anika M S Hartz, Jessica Bernard, Andrea Wolf, André Kachlmeier, Anne Mahringer, Sascha Weggen, Jens Pahnke, Claus U Pietrzik

Open access · greenAbstract read
In one paragraph

Article in Brain, behavior, and immunity, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed
4.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

90 citing papers in PubMed, 131 citations in OpenAlex.

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  11. hLife · 2026
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  20. The blood-brain barrier: a help and a hindrance.Brain : a journal of neurology · 2025
    Review

30 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 7 institutions in 4 countries.

Steffen E StorckInstitute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Anika M S HartzSanders-Brown Center on Aging, University of Kentucky, Lexington, KY, United States; Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY, United States.
Jessica BernardInstitute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Andrea WolfDepartment of Pharmacy Practice and Pharmaceutical Sciences, College of Pharmacy, University of Minnesota, Duluth, MN, United States.
André KachlmeierInstitute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Anne MahringerInstitute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Germany.
Sascha WeggenDepartment of Neuropathology, Heinrich Heine University Duesseldorf, Duesseldorf, Germany.
Jens PahnkeUniversity of Oslo (UiO) & Oslo University Hospital (OUS), Department of Neuro-/Pathology, Oslo, Norway; University of Lübeck (UzL), LIED, Lübeck, Germany; Leibniz-Institute of Plant Biochemistry (IPB), Department for Bioorganic Chemistry, Halle, Germany; University of Latvia (UL), Department of Pharmacology, Riga, Latvia.
Claus U PietrzikInstitute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany. Electronic address: pietrzik@uni-mainz.de.
Johannes Gutenberg University Mainz · DEUniversity Medical Center of the Johannes Gutenberg University Mainz · DEHeidelberg University · DEHeinrich Heine University Düsseldorf · DEUniversity of Kentucky · USUniversity of Latvia · LVUniversity of Minnesota, Duluth · US

Funding

Restoring Blood-Brain Function to Improve Cognition in Alzheimer's DiseaseRF1AG039621 · NIA · UNIVERSITY OF KENTUCKY · PI HARTZ, ANIKA M.S. · 2018 to 2018
$2.9M
Blood-brain barrier P-glycoprotein: a new target for Alzheimer's diseaseR01AG039621 · NIA · UNIVERSITY OF MINNESOTA · PI HARTZ, ANIKA M.S. · 2011 to 2015
$1.5M
CIHRNIA NIH HHS R01 AG039621NIA NIH HHS RF1 AG039621
6 · The paper itself

Abstract

The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic hallmark of Alzheimer's disease (AD). The blood-brain barrier (BBB) provides a large surface area and has been shown to be an important mediator for removal of brain Aβ. Both, the ABC transporter P-glycoprotein (ABCB1/P-gp) and the receptor low-density lipoprotein receptor-related protein 1 (LRP1) have been implicated to play crucial roles in Aβ efflux from brain. Here, with immunoprecipitation experiments, co-immunostainings and dual inhibition of ABCB1/P-gp and LRP1, we show that both proteins are functionally linked, mediating a concerted transcytosis of Aβ through endothelial cells. Late-onset AD risk factor Phosphatidylinositol binding clathrin assembly protein (PICALM) is associated with both ABCB1/P-gp and LRP1 representing a functional link and guiding both proteins through the brain endothelium. Together, our results give more mechanistic insight on Aβ transport across the BBB and show that the functional interplay of different clearance proteins is needed for the rapid removal of Aβ from the brain.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsATP Binding Cassette Transporter, Subfamily B, Member 1Blood-Brain BarrierBrainDisease Models, AnimalEndothelial CellsLow Density Lipoprotein Receptor-Related Protein-1MaleMiceMice, KnockoutMonomeric Clathrin Assembly ProteinsPeptide FragmentsPrimary Cell CultureReceptors, LDLAmyloid beta-PeptidesATP Binding Cassette Transporter, Subfamily B, Member 1Low Density Lipoprotein Receptor-Related Protein-1Lrp1 protein, mouseMonomeric Clathrin Assembly ProteinsPeptide FragmentsPICALM protein, mouseReceptors, LDLTumor Suppressor ProteinsABC transporter B1/P-glycoprotein (ABCB1/P-gp)Alzheimer’s disease (AD)Amyloid-beta (Aβ)Blood-brain barrier (BBB)ClearanceEndothelial cellEndotheliumLow-density lipoprotein receptor-related protein 1 (LRP1)Phosphatidylinositol-binding clathrin assembly protein (PICALM)Transcytosis

Identifiers

PMID30041013
PMCPMC7748946
OpenAlexW2884201957

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.