Evidence map›Paper›PMID 28322202›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2017

Genetic epistasis regulates amyloid deposition in resilient aging.

Daniel Felsky, Jishu Xu, Lori B Chibnik, Julie A Schneider, Jo Knight, James L Kennedy, Alzheimer's Disease Neuroimaging Initiative, David A Bennett, Philip L De Jager, Aristotle N Voineskos

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 32% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Religious Orders Study and Rush Memory and Aging Project.Journal of Alzheimer's disease : JAD · 2018
    Review
  6. Letter.Alzheimer's & dementia (Amsterdam, Netherlands) · 2017
    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

10 authors at 4 institutions in 3 countries.

Daniel FelskyCampbell Family Mental Health Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Jishu XuProgram in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Lori B ChibnikProgram in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Julie A SchneiderRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
Jo KnightCampbell Family Mental Health Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Data Science Institute and the Medical School, Lancaster University, Bailrigg, Lancaster, UK.
James L KennedyCampbell Family Mental Health Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Alzheimer's Disease Neuroimaging Initiative
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
Philip L De JagerProgram in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Aristotle N VoineskosCampbell Family Mental Health Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: aristotle.voineskos@camh.ca.
University of Toronto · CABrigham and Women's Hospital · USBroad Institute · USRush University Medical Center · US

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI SCHNEIDER, JULIE A. · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Genetic Epidemiology of Cognitive Decline in an Aging Population SampleR01AG030146 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI EVANS, DENIS A · 2007 to 2018
$6.2M
Risk Factors, Pathology, and Clinical Expressions of ADRF1AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2014 to 2014
$6.0M
Mechanisms linking insulin resistance to brain structure, pathology, and functionR01NS084965 · NINDS · RUSH UNIVERSITY MEDICAL CENTER · PI AHIMA, REXFORD S., ARNOLD, STEVEN E · 2014 to 2018
$3.2M
Integrative analysis of genomic and epigenomic architecture in cognitive declineK25AG041906 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI CHIBNIK, LORI BETH · 2012 to 2016
$771k
NIA NIH HHS K25 AG041906NIA NIH HHS P30 AG010161NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG030146NIA NIH HHS RF1 AG015819NINDS NIH HHS R01 NS084965
6 · The paper itself

Abstract

introductionThe brain-derived neurotrophic factor (BDNF) interacts with important genetic Alzheimer's disease (AD) risk factors. Specifically, variants within the SORL1 gene determine BDNF's ability to reduce amyloid β (Aβ) in vitro. We sought to test whether functional BDNF variation interacts with SORL1 genotypes to influence expression and downstream AD-related processes in humans.

methodsWe analyzed postmortem brain RNA sequencing and neuropathological data for 441 subjects from the Religious Orders Study/Memory and Aging Project and molecular and structural neuroimaging data for 1285 subjects from the Alzheimer's Disease Neuroimaging Initiative.

resultsWe found one SORL1 RNA transcript strongly regulated by SORL1-BDNF interactions in elderly without pathological AD and showing stronger associations with diffuse than neuritic Aβ plaques. The same SORL1-BDNF interactions also significantly influenced Aβ load as measured with [ DISCUSSION: Our results bridge the gap between risk and resilience factors for AD, demonstrating interdependent roles of established SORL1 and BDNF functional genotypes.

Indexed as

AgingAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAniline CompoundsAnisotropyAutopsyBrainBrain-Derived Neurotrophic FactorCohort StudiesEpistasis, GeneticEthylene GlycolsFemaleGenetic Predisposition to DiseaseGenotypeAmyloid beta-PeptidesAniline CompoundsBrain-Derived Neurotrophic FactorEthylene GlycolsflorbetapirLDL-Receptor Related ProteinsMembrane Transport ProteinsSORL1 protein, humanAlzheimer's diseaseAmyloidBDNFEpistasisPET imagingRNA sequencingSORL1

Identifiers

PMID28322202
PMCPMC5601013
OpenAlexW2595650687

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.