Evidence map›Paper›PMID 38326859›Full record

ArticleAlzheimer's research & therapy2024

DNA hypomethylation promotes the expression of CASPASE-4 which exacerbates inflammation and amyloid-β deposition in Alzheimer's disease.

Kylene P Daily, Asmaa Badr, Mostafa Eltobgy, Shady Estfanous, Owen Whitham, Michelle H Tan, Cierra Carafice, Kathrin Krause, Andrew McNamara, Kaitlin Hamilton and 14 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

13 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Post-translational modifications regulating microglial inflammation in central nervous system disorders: a review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Cells · 2025
    Article
  9. Review
  10. DNA Methylation in Alzheimer's Disease.Current topics in behavioral neurosciences · 2025
    Review
  11. Review
  12. Review
  13. 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

24 authors at 2 institutions in 4 countries.

Kylene P DailyDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA.
Asmaa BadrDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA.
Mostafa EltobgyDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA.
Shady EstfanousDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA.
Owen WhithamDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA.
Michelle H TanDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA.
Cierra CaraficeDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA.
Kathrin KrauseDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA.
Andrew McNamaraDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA.
Kaitlin HamiltonDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA.
Samuel HouleDepartment of Neuroscience, The Ohio State University, Columbus, OH, 43210, USA.
Spandan GuptaDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA.
Gauruv A GuptaDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA.
Shruthi MadhuDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA.
Julie FitzgeraldDepartment of Neuroscience, The Ohio State University, Columbus, OH, 43210, USA.
Abbey A SaadeyDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA.
Brooke LasterDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA.
Pearlly YanGenomics Shared Resource, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Amy WebbDepartment of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.
Xiaoli ZhangCenter for Biostatistics, Ohio State University, Columbus, OH, USA.
Maciej PietrzakDepartment of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.
Olga N Kokiko-CochranDepartment of Neuroscience, The Ohio State University, Columbus, OH, 43210, USA.
Hazem E GhoneimDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA. hazem.ghoneim@osumc.edu.
Amal O AmerDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA. amal.amer@osumc.edu.
The Ohio State University · USHelwan University · EG

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3M
The OSU Center for Clinical and Translational Science: Advancing Today's Discoveries to Improve HealthUM1TR004548 · NCATS · OHIO STATE UNIVERSITY · PI CYNTHIA A GERHARDT, JULIE A. JOHNSON · 2023 to 2026
$22.0M
Mouse CoreP30NS045713 · NINDS · BRANDEIS UNIVERSITY · PI ROSBASH, MICHAEL · 2003 to 2013
$7.8M
THE ROLE OF THE NON-CANONICAL INFLAMMASOME IN INNATE IMMUNITYR01AI159452 · NIAID · OHIO STATE UNIVERSITY · PI AMER, AMAL O, SEVEAU, STEPHANIE M M · 2021 to 2025
$3.7M
Host Responses to the Pore-Forming Toxin Listeriolysin OR01AI157205 · NIAID · OHIO STATE UNIVERSITY · PI AMER, AMAL O, BOYAKA, PROSPER N · 2021 to 2025
$3.2M
Targeting specific MicroRNA to alleviate Alzheimer’s Disease pathobiologyR01AG082113 · NIA · OHIO STATE UNIVERSITY · PI Amal O Amer · 2023 to 2026
$2.7M
Enhancing the Effectiveness of Immunotherapies by T Cell Epigenetic ReprogrammingR01AI170926 · NIAID · OHIO STATE UNIVERSITY · PI Hazem E. Ghoneim · 2023 to 2026
$2.6M
Resue of CF phagocyte function with CFTR modulator therapyR01HL158747 · NHLBI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI GUGLANI, LOKESH, KOPP, BENJAMIN T · 2022 to 2025
$2.1M
The role of microRNA-calibrated autophagy in innate immunity and inflammationR01HL127651 · NHLBI · OHIO STATE UNIVERSITY · PI AMER, AMAL O, CORMET-BOYAKA, ESTELLE A · 2015 to 2018
$1.5M
Interdisciplinary Program in Microbe-Host BiologyT32AI165391 · NIAID · OHIO STATE UNIVERSITY · PI RAJENDAR K DEORA, Daniel J Wozniak · 2022 to 2026
$1.5M
Alzheimer’s Disease Biomarker for Diagnosis and PrognosisR21AG067755 · NIA · OHIO STATE UNIVERSITY · PI AMER, AMAL O, TARAWNEH, RAWAN · 2020 to 2021
$417k
Mechanistic basis of inflammation in Alzheimers DiseaseR21AG064899 · NIA · OHIO STATE UNIVERSITY · PI AMER, AMAL O · 2020 to 2021
$409k
NCATS NIH HHS UM1 TR004548NCI NIH HHS P30 CA016058NHLBI NIH HHS R01 HL127651NHLBI NIH HHS R01 HL158747NIAID NIH HHS R01 AI157205NIAID NIH HHS R01 AI159452NIAID NIH HHS R01 AI170926NIAID NIH HHS T32 AI165391NIA NIH HHS R01 AG082113NIA NIH HHS R21 AG064899NIA NIH HHS R21 AG067755NINDS NIH HHS P30 NS045713
6 · The paper itself

Abstract

Alzheimer's disease (AD) is the sixth leading cause of death in the USA. It is established that neuroinflammation contributes to the synaptic loss, neuronal death, and symptomatic decline of AD patients. Accumulating evidence suggests a critical role for microglia, innate immune phagocytes of the brain. For instance, microglia release pro-inflammatory products such as IL-1β which is highly implicated in AD pathobiology. The mechanisms underlying the transition of microglia to proinflammatory promoters of AD remain largely unknown. To address this gap, we performed reduced representation bisulfite sequencing (RRBS) to profile global DNA methylation changes in human AD brains compared to no disease controls. We identified differential DNA methylation of CASPASE-4 (CASP4), which when expressed promotes the generation of IL-1β and is predominantly expressed in immune cells. DNA upstream of the CASP4 transcription start site was hypomethylated in human AD brains, which was correlated with increased expression of CASP4. Furthermore, microglia from a mouse model of AD (5xFAD) express increased levels of CASP4 compared to wild-type (WT) mice. To study the role of CASP4 in AD, we developed a novel mouse model of AD lacking the mouse ortholog of CASP4 and CASP11, which is encoded by mouse Caspase-4 (5xFAD/Casp4

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesCaspases, InitiatorAnimalsDisease Models, AnimalDNA MethylationHumansInflammationMiceMice, TransgenicMicrogliaAmyloid beta-PeptidesCasp4 protein, mouseCaspases, InitiatorAlzheimer’s diseaseAmyloid-βCaspase-11Caspase-4IL-1βInflammasomeInflammationMethylationNeuroinflammation

Identifiers

PMID38326859
PMCPMC10851453
OpenAlexW4391648738

What OpenQuestion holds

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LicenceCC BY
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.