Evidence map›Paper›PMID 30517207›Full record

ArticlePloS one2018

Longer TOMM40 poly-T variants associated with higher FDDNP-PET medial temporal tau and amyloid binding.

Prabha Siddarth, Alison C Burggren, David A Merrill, Linda M Ercoli, Zanjbeel Mahmood, Jorge R Barrio, Gary W Small

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.4field-weighted citation impact, top 35% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. International journal of molecular sciences · 2023
    Article
  4. Article
  5. Article
  6. Redox signaling and metabolism in Alzheimer's disease.Frontiers in aging neuroscience · 2022
    Review
  7. Article
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

7 authors at 2 institutions in 1 country.

Prabha SiddarthDepartment of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, United States of America.ORCID 0000-0001-8746-6353
Alison C BurggrenCenter for Cognitive Neurosciences, UCLA, Los Angeles, United States of America.
David A MerrillDepartment of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, United States of America.
Linda M ErcoliDepartment of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, United States of America.
Zanjbeel MahmoodSan Diego State University/University of California, San Diego Joint Doctoral Program in Clinical Psychology, United States of America.
Jorge R BarrioDepartment of Molecular & Medical Pharmacology, UCLA, Los Angeles, United States of America.
Gary W SmallDepartment of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, United States of America.
San Diego State University · USUniversity of Oregon · US

Funding

ZDV &3TC NEVIRAPINE COMBINATION THERAPY IN HIV 1 INFECTED INFANTS &M01RR000865 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WASHINGTON, ARNOLD E. · 1985 to 2011
$43.4M
UCLA ALZHEIMERS DISEASE RESEARCH CENTERP50AG016570 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BREDESEN, DALE E. · 1999 to 2014
$25.9M
VISUALIZING BRAIN A-BETA, TAU /SEROTONIN RECEPTOR DENSITP01AG025831 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SMALL, GARY WILLIAM · 2005 to 2010
$7.0M
FUNCTIONAL MRI FOR EARLY DIAGNOSIS OF ALZHEIMER'SR01AG013308 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BOOKHEIMER, SUSAN Y · 1995 to 2011
$4.5M
Effects of heavy adolescent cannabis use on brain morphology in agingK01DA034728 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BURGGREN, ALISON CLEMENTS · 2013 to 2017
$776k
UCLA ALZHEIMERS DISEASE CENTERP30AG010123 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CUMMINGS, JEFFREY L. · 1991 to 1998
–
FUNCTIONAL BRAIN IMAGING AND MENTAL DISORDERS IN AGINGR01MH052453 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SMALL, GARY WILLIAM · 1995 to 1999
–
NCRR NIH HHS M01 RR000865NIA NIH HHS P01 AG025831NIA NIH HHS P30 AG010123NIA NIH HHS P50 AG016570NIA NIH HHS R01 AG013308NIDA NIH HHS K01 DA034728NIMH NIH HHS R01 MH052453
6 · The paper itself

Abstract

backgroundThe translocase of outer mitochondrial membrane 40 (TOMM40), which lies in linkage disequilibrium with the apolipoprotein E (APOE) gene, has been implicated in Alzheimer's disease (AD). TOMM40 influences AD pathology through mitochondrial neurotoxicity, and the medial temporal lobe (MTL) is the most likely brain region for identifying early manifestations of AD-related morphology changes. While early reports indicated that the longer length poly-T allele of TOMM40 increases risk for AD, these findings have not been consistently replicated in further studies. We examined the effect of TOMM40 and APOE on regional brain positron emission tomography (PET) 2-(1-{6-[(2 [F18]fluoroethyl) (methyl) amino]-2-naphthyl}ethylidene)malononitrile (FDDNP) binding values in MTL.

methodsA total of 73 non-demented older adults (42 females; mean age: 62.9(10.9) completed genotyping for both APOE and TOMM40 and received FDDNP-PET scans. For TOMM40, the lengths of the poly-T sequence were classified as short (14-20 repeats; S), long (21-29 repeats, L) or very long (>29 repeats, VL). Using general linear models, we examined medial temporal lobe FDDNP binding and cognitive functioning between TOMM40 and APOE-4 groups, with age, sex, and education as covariates.

resultsData from 30 individuals with APOE-4 and L TOMM40 poly-T length, 11 non E4 TOMM40 S/S, 14 non E4 TOMM40 S/VL and 13 non E4 TOMM40 VL/VL were analyzed. Medial temporal FDDNP binding differed significantly between TOMM40/APOE groups (F(3,62) = 3.3,p = .03). Participants with TOMM40 S/S exhibited significantly lower binding compared to TOMM40 S/VL and APOE-4 carriers. We did not find a significant relationship between TOMM40 poly-T lengths/APOE risk groups and cognitive functioning.

conclusionsThis is the first report to demonstrate a significant association between longer TOMM40 poly-T lengths and higher medial temporal plaque and tangle burden in non-demented older adults. Identifying biomarkers that are risk factors for AD will enhance our ability to identify subjects likely to benefit from novel AD treatments.

Indexed as

AgedAged, 80 and overAllelesAlzheimer DiseaseApolipoprotein E4FemaleHumansMaleMembrane Transport ProteinsMiddle AgedMitochondrial Precursor Protein Import Complex ProteinsNeuropsychological TestsPlaque, AmyloidPoly TPositron-Emission TomographyApolipoprotein E4Membrane Transport ProteinsMitochondrial Precursor Protein Import Complex ProteinsPoly TTOMM40 protein, human

Identifiers

PMID30517207
PMCPMC6281258
OpenAlexW2902531485

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.