Evidence map›Paper›PMID 28768149›Full record

ArticleBiochimica et biophysica acta. Molecular basis of disease2017

The biological foundation of the genetic association of TOMM40 with late-onset Alzheimer's disease.

Kahli Zeitlow, Lefko Charlambous, Isaac Ng, Sonal Gagrani, Mirta Mihovilovic, Shuhong Luo, Daniel L Rock, Ann Saunders, Allen D Roses, W Kirby Gottschalk

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochimica et biophysica acta. Molecular basis of disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 9% 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

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.

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  12. International journal of molecular sciences · 2023
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  15. Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Kahli ZeitlowDuke University, Department of Neurology, USA. Electronic address: Kahli.zeitlow@Duke.edu.
Lefko CharlambousDuke University, Department of Neurology, USA. Electronic address: Lefko.Charlambous@Duke.edu.
Isaac NgDuke University, Department of Neurology, USA.
Sonal GagraniDuke University, Department of Neurology, USA.
Mirta MihovilovicDuke University, Department of Neurology, USA. Electronic address: mihov001@bellsouth.net.
Shuhong LuoDepartment of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
Daniel L RockDepartment of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
Ann SaundersZinfandel Pharmaceuticals, Inc., USA. Electronic address: asaunders@zinfandelpharma.com.
Allen D RosesDuke University, Department of Neurology, USA; Zinfandel Pharmaceuticals, Inc., USA.
W Kirby GottschalkDuke University, Department of Neurology, USA. Electronic address: Kirby.Gottschalk@Duke.edu.
Duke University · USUniversity of Illinois Urbana-Champaign · US

Funding

Role of the TOMM40 poly-T variant in the pathogenesis of Alzheimer's diseaseR01AG040370 · NIA · DUKE UNIVERSITY · PI CHIBA-FALEK, ORNIT · 2013 to 2017
$2.2M
NIA NIH HHS R01 AG040370
6 · The paper itself

Abstract

A variable-length poly-T variant in intron 6 of the TOMM40 gene, rs10524523, is associated with risk and age-of-onset of sporadic (late-onset) Alzheimer's disease. In Caucasians, the three predominant alleles at this locus are Short (S), Long (L) or Very long (VL). On an APOE ε3/3 background, the S/VL and VL/VL genotypes are more protective than S/S. The '523 poly-T has regulatory properties, in that the VL poly-T results in higher expression than the S poly-T in luciferase expression systems. The aim of the current work was to identify effects on cellular bioenergetics of increased TOM40 protein expression. MitoTracker Green fluorescence and autophagic vesicle staining was the same in control and over-expressing cells, but TOM40 over-expression was associated with increased expression of TOM20, a preprotein receptor of the TOM complex, the mitochondrial chaperone HSPA9, and PDHE1a, and increased activities of the oxidative phosphorylation complexes I and IV and of the TCA member α-ketoglutaric acid dehydrogenase. Consistent with the complex I findings, respiration was more sensitive to inhibition by rotenone in control cells than in the TOM40 over-expressing cells. In the absence of inhibitors, total cellular ATP, the mitochondrial membrane potential, and respiration were elevated in the over-expressing cells. Spare respiratory capacity was greater in the TOM40 over-expressing cells than in the controls. TOM40 over-expression blocked Ab-elicited decreases in the mitochondrial membrane potential, cellular ATP levels, and cellular viability in the control cells. These data suggest elevated expression of TOM40 may be protective of mitochondrial function.

Indexed as

Alzheimer DiseaseGene Expression RegulationMembrane Transport ProteinsMitochondriaApolipoproteins EElectron Transport Complex IFemaleGenetic LociHeLa CellsHSP70 Heat-Shock ProteinsHumansKetoglutarate Dehydrogenase ComplexMembrane Potential, MitochondrialMitochondrial Precursor Protein Import Complex ProteinsMitochondrial ProteinsReceptors, Cell SurfaceApolipoproteins EElectron Transport Complex IHSP70 Heat-Shock ProteinsHSPA9 protein, humanKetoglutarate Dehydrogenase ComplexMembrane Transport ProteinsMitochondrial Precursor Protein Import Complex ProteinsMitochondrial ProteinsReceptors, Cell SurfaceTOMM20 protein, humanTOMM40 protein, humanAlzheimer'sEnergeticsMitochondriaNeurodegenerationTOMTOMM40

Identifiers

PMID28768149
PMCPMC5659897
OpenAlexW2739591311

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.