Evidence map›Paper›PMID 15975076›Full record

ArticleCurrent Alzheimer research2004

The role of P-glycoprotein in cerebral amyloid angiopathy; implications for the early pathogenesis of Alzheimer's disease.

Silke Vogelgesang, Rolf W Warzok, Ingolf Cascorbi, Christiane Kunert-Keil, Eike Schroeder, Heyo K Kroemer, Werner Siegmund, Lary C Walker, Jens Pahnke

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Current Alzheimer research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 2 pooled it
2.0field-weighted citation impact, top 13% 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

76 citing papers in PubMed, 2 syntheses or guidelines pooled it, 164 citations in OpenAlex.

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  20. Pharmacokinetic Modeling of [Molecular pharmaceutics · 2020
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16 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 2 institutions in 2 countries.

Silke VogelgesangDepartment of Neuropathology, University of Greifswald, Germany.
Rolf W Warzok
Ingolf Cascorbi
Christiane Kunert-Keil
Eike Schroeder
Heyo K Kroemer
Werner Siegmund
Lary C Walker
Jens Pahnke
Universität Greifswald · DEUniversity Hospital of Zurich · CH

Funding

YNPRC NHP CLINICAL MEDICINE RESIDENCY PROGRAM - SUPPLEMENTP51RR000165 · NCRR · EMORY UNIVERSITY · PI ALTMAN, JOHN DAVID · 1985 to 2011
$114.0M
NCRR NIH HHS P51 RR000165
6 · The paper itself

Abstract

It has been shown in vitro that beta-amyloid (Abeta) is transported by P-glycoprotein (P-gp). Previously, we demonstrated that Abeta immunoreactivity is significantly elevated in brain tissue of individuals with low expression of P-gp in vascular endothelial cells. These findings led us to hypothesize that P-gp might be involved in the clearance of Abeta in normal aging and particularly in Alzheimer's disease (AD). As we were interested in the early pathogenesis of Abeta deposition, we studied the correlation between cerebral amyloid angiopathy (CAA) and P-gp expression in brain tissue samples from 243 non-demented elderly cases (aged 50 to 91 years). We found that endothelial P-gp and vascular Abeta were never colocalized, i.e., vessels with high P-gp expression showed no Abeta deposition in their walls, and vice versa. Abeta deposition occurred first in arterioles where P-gp expression was primarily low, and disappeared completely with the accumulation of Abeta. At this early stage, P-gp was upregulated in capillaries, suggesting a compensatory mechanism to increase Abeta clearance from the brain. Capillaries were usually affected only at later stages of CAA, at which point P-gp was lost even in these vessels. We hypothesize that Abeta clearance may be altered in individuals with diminished P-gp expression due, e.g., to genetic or environmental effects (such as drug administration). The impairment of Abeta clearance could lead to the accumulation and earlier deposition of Abeta, both in the walls of blood vessels and in the brain parenchyma, thus elevating the risk of CAA and AD.

Indexed as

AgedAged, 80 and overAgingAlzheimer DiseaseAmyloid beta-PeptidesATP Binding Cassette Transporter, Subfamily B, Member 1Blood VesselsBrainCerebral Amyloid AngiopathyFemaleHumansMaleMiddle AgedProtein IsoformsRisk FactorsTissue DistributionAmyloid beta-PeptidesATP Binding Cassette Transporter, Subfamily B, Member 1Protein Isoforms

Identifiers

PMID15975076
PMCPMC2763541
OpenAlexW2142878553

What OpenQuestion holds

Textmetadata
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.