Evidence map›Paper›PMID 34482628›Full record

SynthesisAlzheimer's & dementia : the journal of the Alzheimer's Association2022

Epigenomic features related to microglia are associated with attenuated effect of APOE ε4 on Alzheimer's disease risk in humans.

Yiyi Ma, Lei Yu, Marta Olah, Rebecca Smith, Stephanie R Oatman, Mariet Allen, Ehsan Pishva, Bin Zhang, Vilas Menon, Nilüfer Ertekin-Taner and 4 more

Open access · greenAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 2 pooled it
1.1field-weighted citation impact, top 24% 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

10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 16 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. The Influence of Kynurenine Metabolites on Neurodegenerative Pathologies.International journal of molecular sciences · 2024
    Review
  9. Omics-based biomarkers discovery for Alzheimer's disease.Cellular and molecular life sciences : CMLS · 2022
    Review
  10. Epigenetics in Alzheimer's Disease.Frontiers in aging neuroscience · 2022
    Review
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

14 authors at 7 institutions in 2 countries.

Yiyi MaCenter for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, New York, USA.
Lei YuRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Marta OlahCenter for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, New York, USA.
Rebecca SmithCollege of Medicine and Health, University of Exeter Medical School, Exeter University, Exeter, UK.
Stephanie R OatmanDepartment of Neuroscience, Mayo Clinic Florida, Jacksonville, Florida, USA.
Mariet AllenDepartment of Neuroscience, Mayo Clinic Florida, Jacksonville, Florida, USA.
Ehsan PishvaCollege of Medicine and Health, University of Exeter Medical School, Exeter University, Exeter, UK.
Bin ZhangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Vilas MenonCenter for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, New York, USA.
Nilüfer Ertekin-TanerDepartment of Neuroscience, Mayo Clinic Florida, Jacksonville, Florida, USA.
Katie LunnonCollege of Medicine and Health, University of Exeter Medical School, Exeter University, Exeter, UK.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Hans-Ulrich KleinCenter for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, New York, USA.
Philip L De JagerCenter for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, New York, USA.
Columbia University Irving Medical Center · USUniversity of Exeter · GBJacksonville College · USRush University Medical Center · USBroad Institute · USIcahn School of Medicine at Mount Sinai · USMayo Clinic in Florida · US

Funding

Vascular Structure and Function in Cognitive AgingP01AG003949 · NIA · YESHIVA UNIVERSITY · PI Charles B Hall · 1985 to 2026
$73.9M
SUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 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
VESICULAR LOCALIZATION AND FUNCTION OF PRESENILIN 1 FRAGMENTP50AG005138 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI GROSSMAN, HILLEL · 1985 to 2019
$37.9M
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI PETERSEN, RONALD C · 1999 to 2018
$36.9M
Research Education ComponentP30AG062677 · NIA · MAYO CLINIC ROCHESTER · PI NILUFER ERTEKIN-TANER · 2019 to 2026
$33.5M
Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5M
Integrative Network Biology Approaches to Identify, Characterize and Validate Molecular Subtypes in Alzheimer's DiseaseU01AG046170 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WANG, MINGHUI, ZHANG, BIN · 2013 to 2022
$26.0M
Risk Factors for Incident Alzheimer's Disease in a Biracial CommunityR01AG011101 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI EVANS, DENIS A · 1993 to 2010
$24.7M
Integrating the exposome and methylome to inform brain molecular changes in ADRD across established diverse cohorts.U01AG046139 · NIA · UNIVERSITY OF FLORIDA · PI ERTEKIN-TANER, NILUFER, FUNK, CORY · 2013 to 2022
$24.6M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Arizona Biomedical Research Commission 0011Arizona Biomedical Research Commission 05-901Arizona Biomedical Research Commission 1001Arizona Biomedical Research Commission 4001Arizona Department of Health Services 211002NCRR NIH HHS KL2 RR024151NIA NIH HHS K08 AG034290NIA NIH HHS K25 AG041906NIA NIH HHS P01 AG002219NIA NIH HHS P01 AG003949NIA NIH HHS P01 AG017216NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG062677NIA NIH HHS P30 AG19610NIA NIH HHS P50 AG005138NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG025711NIA NIH HHS R01 AG011101NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG018023NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG032990NIA NIH HHS R01 AG036042NIA NIH HHS R01 AG036836NIA NIH HHS R01 AG042210NIA NIH HHS R01 AG043617NIA NIH HHS R01 AG061796NIA NIH HHS RC2 AG036547NIA NIH HHS RF1 AG036042NIA NIH HHS RF1 AG057440NIA NIH HHS U01 AG006786NIA NIH HHS U01 AG046139NIA NIH HHS U01 AG046170NIA NIH HHS U01 AG061356NIEHS NIH HHS U01 ES017155NIMH NIH HHS R01 MH064673NINDS NIH HHS R01 NS080820NINDS NIH HHS U24 NS072026US National Institutes of Health K25 AG04190601US National Institutes of Health P30 AG10161US National Institutes of Health R01 AG11101US National Institutes of Health R01 AG15819US National Institutes of Health R01 AG17917US National Institutes of Health R01 AG18023US National Institutes of Health R01 AG30146US National Institutes of Health U01AG61356
6 · The paper itself

Abstract

Not all apolipoprotein E (APOE) ε4 carriers who survive to advanced age develop Alzheimer's disease (AD); factors attenuating the risk of ε4 on AD may exist. Guided by the top ε4-attenuating signals from methylome-wide association analyses (N = 572, ε4+ and ε4-) of neurofibrillary tangles and neuritic plaques, we conducted a meta-analysis for pathological AD within the ε4+ subgroups (N = 235) across four independent collections of brains. Cortical RNA-seq and microglial morphology measurements were used in functional analyses. Three out of the four significant CpG dinucleotides were captured by one principal component (PC1), which interacts with ε4 on AD, and is associated with expression of innate immune genes and activated microglia. In ε4 carriers, reduction in each unit of PC1 attenuated the odds of AD by 58% (odds ratio = 2.39, 95% confidence interval = [1.64,3.46], P = 7.08 × 10

Indexed as

Alzheimer DiseaseApolipoprotein E4AllelesApolipoproteins EEpigenomicsGenotypeHumansMicrogliaNeurofibrillary TanglesApolipoprotein E4Apolipoproteins EAlzheimer's diseaseapolipoprotein Eepigenomemicroglia

Identifiers

PMID34482628
PMCPMC9475136
OpenAlexW3110893574

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.