Evidence map›Paper›PMID 39356058›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024

Widespread transposable element dysregulation in human aging brains with Alzheimer's disease.

Yayan Feng, Xiaoyu Yang, Yuan Hou, Yadi Zhou, James B Leverenz, Charis Eng, Andrew A Pieper, Alison Goate, Yin Shen, Feixiong Cheng

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Review
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  9. Widespread transposable element dysregulation in human aging brains with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    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.

Yayan FengCleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Xiaoyu YangCleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Yuan HouCleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Yadi ZhouCleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
James B LeverenzLou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Charis EngGenomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Andrew A PieperDepartment of Psychiatry, Case Western Reserve University, Cleveland, Ohio, USA.
Alison GoateDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Yin ShenInstitute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
Feixiong ChengCleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Funding

Vascular Structure and Function in Cognitive AgingP01AG003949 · NIA · YESHIVA UNIVERSITY · PI Richard B. LIPTON · 1985 to 2026
$73.9M
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
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 BENNETT, DAVID ALAN · 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
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI BU, GUOJUN · 1999 to 2018
$36.9M
Research Education ComponentP30AG066514 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Carolyn Wei Zhu · 2020 to 2026
$31.0M
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
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, PETERS, METTE · 2013 to 2022
$24.6M
Translational and Therapeutics CoreP30AG072959 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI JAGAN AYYAPPAN PILLAI · 2021 to 2026
$23.9M
Renewal of Centers of Biomedical Research Excellence (COBRE) (Phase 2) CNTN - ResubmissionP20GM109025 · NIGMS · CLEVELAND CLINIC FOUNDATION · PI JESSICA KIRKLAND CALDWELL · 2015 to 2026
$22.8M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Alzheimer's Association ALZDISCOVERY-1051936Alzheimer's Drug Discovery FoundationBLRD VA I01 BX005976Department of Veterans Affairs Merit Award I01BX005976Illinois Department of Public HealthNational Institute of Neurological Disorders and Stroke (NINDS) RF1NS133812National Institute on Aging (NIA) P30AG072959National Institute on Aging (NIA) R01AG066707National Institute on Aging (NIA) R01AG076448National Institute on Aging (NIA) R01AG079291National Institute on Aging (NIA) R01AG082118National Institute on Aging (NIA) R01AG084250National Institute on Aging (NIA) R21AG083003National Institute on Aging (NIA) R56AG074001National Institute on Aging (NIA) RF1AG079557National Institute on Aging (NIA) RF1AG082211National Institute on Aging (NIA) U01AG073323NIA NIH HHS K08 AG065463NIA NIH HHS P01 AG003949NIA NIH HHS P01 AG017216NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG062428NIA NIH HHS P30 AG066514NIA NIH HHS P30 AG072959NIA NIH HHS P30AG10161NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG025711NIA NIH HHS R01 AG003949NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017216NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG018023NIA NIH HHS R01 AG025711NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG032990NIA NIH HHS R01 AG036836NIA NIH HHS R01 AG066707NIA NIH HHS R01 AG076448NIA NIH HHS R01 AG079291NIA NIH HHS R01 AG082118NIA NIH HHS R01 AG084250NIA NIH HHS R01AG15819NIA NIH HHS R01AG17917NIA NIH HHS R01AG30146NIA NIH HHS R01AG36836NIA NIH HHS R21 AG083003NIA NIH HHS R56 AG074001NIA NIH HHS RF1 AG079557NIA NIH HHS RF1 AG082211NIA NIH HHS U01 AG006576NIA NIH HHS U01 AG006786NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG046139NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG046170NIA NIH HHS U01AG046170NIA NIH HHS U01 AG061356NIA NIH HHS U01 AG073323NIA NIH HHS U01AG32984NIA NIH HHS U01AG46152NIA NIH HHS U01AG61356NIGMS NIH HHS P20 GM109025NINDS NIH HHS R01 NS080820NINDS NIH HHS RF1 NS133812the American Heart Association and Paul Allen Foundation Initiative in Brain Health and Cognitive Impairment 19PABH134580006the Louis Stokes VA Medical Center resources and facilitiesthe Morley-Mather Chair in Neuropsychiatry of University Hospitals of Cleveland Medical Centerthe Rebecca E. Barchas MD Chair in Translational Psychiatry of Case Western Reserve UniversityThe Valour Foundation
6 · The paper itself

Abstract

introductionTransposable element (TE) dysregulation is associated with neuroinflammation in Alzheimer's disease (AD) brains. Yet, TE quantitative trait loci (teQTL) have not been well characterized in human aged brains with AD.

methodsWe leveraged large-scale bulk and single-cell RNA sequencing, whole-genome sequencing (WGS), and xQTL from three human AD brain biobanks to characterize TE expression dysregulation and experimentally validate AD-associated TEs using CRISPR interference (CRISPRi) assays in human induced pluripotent stem cell (iPSC)-derived neurons.

resultsWe identified 26,188 genome-wide significant TE expression QTLs (teQTLs) in human aged brains. Subsequent colocalization analysis of teQTLs with AD genetic loci identified AD-associated teQTLs and linked locus TEs. Using CRISPRi assays, we pinpointed a neuron-specific suppressive role of the activated short interspersed nuclear element (SINE; chr11:47608036-47608220) on expression of C1QTNF4 via reducing neuroinflammation in human iPSC-derived neurons. DISCUSSION: We identified widespread TE dysregulation in human AD brains and teQTLs offer a complementary analytic approach to identify likely AD risk genes. HIGHLIGHTS: Widespread transposable element (TE) dysregulations are observed in human aging brains with degrees of neuropathology, apolipoprotein E (APOE) genotypes, and neuroinflammation in Alzheimer's disease (AD). A catalog of TE quantitative trait loci (teQTLs) in human aging brains was created using matched RNA sequencing and whole-genome sequencing data. CRISPR interference assays reveal that an upregulated intergenic TE from the MIR family (chr11: 47608036-47608220) suppresses expression of its nearest anti-inflammatory gene C1QTNF4 in human induced pluripotent stem cell-derived neurons.

Indexed as

AgingAlzheimer DiseaseBrainDNA Transposable ElementsInduced Pluripotent Stem CellsQuantitative Trait LociAgedFemaleGenome-Wide Association StudyHumansMaleNeuronsWhole Genome SequencingDNA Transposable ElementsAlzheimer's diseaseCRISPR interferenceneuroinflammationtransposable element expression quantitative trait locitransposable elements

Identifiers

PMID39356058
PMCPMC11567813

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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.