OSCR

Sex-specific regulation of angiogenin in Alzheimer's disease.

Overview

Authors: Marko Jörg1, Lukas Walz1, Sebastian Nathal1, Marco Kristen1, Christine Lietz1, Max Müller1, Vu Thu Thuy Nguyen2, Nicolas Ruffini3, Marie-Luise Winz1, Susanne Gerber3, Kristina Endres2,4, Mark Helm1, Kristina Friedland1
ORCID iDs: Marko Jörg, Max Müller, Nicolas Ruffini, Marie-Luise Winz, Susanne Gerber, Kristina Endres, Kristina Friedland
  1. Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University,Mainz, Germany
  2. Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg University,Mainz, Germany
  3. Institute of Human Genetics, University Medical Center Johannes Gutenberg University,Mainz, Germany
  4. Campus Zweibrücken, University of Applied Sciences Kaiserslautern,Zweibrücken, Germany
Institutions: Johannes Gutenberg University Mainz (Germany); University of Applied Sciences Kaiserslautern (Germany)
Journal: Molecular psychiatry, volume 31, issue 10, pages 5735-5748
Dates: received 12 September 2025; accepted 20 May 2026; published online 2 June 2026; in print 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41380-026-03656-7 · PMID 42230965 · PMCID PMC13569426 · OpenAlex W7163171687
Open access: hybrid, a free copy (OpenAlex)
Status: data only
Categories: human (organism), mouse (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Statistics
Keywords: Neuroscience, Psychiatric disorders
MeSH: Alzheimer Disease*, Ribonuclease, Pancreatic*, Animals, Apoptosis, Brain, Disease Models, Animal, Female, Humans, Inflammation, Male, Mice, Neurons (* major topic)
Topic: Alzheimer's disease research and treatments (Physiology, Medicine), according to OpenAlex
Funding: TRR319 RMaP seed funding; NeurodegX of the MWG Rhineland-Palatinate; Deutsche Forschungsgemeinschaft (DFG) (TRR319 RMaP (Project Id 439669440) TPB05, TRR319 RMaP (Project Id 439669440) TP A05)
Citations: not cited yet (Europe PMC); 85 references in the paper

Abstract

Alzheimer’s disease (AD) is a heterogeneous neurodegenerative disorder, highlighting the need to identify novel molecular regulators for effective treatment development. Angiogenin (ANG), a stress-responsive ribonuclease that inhibits apoptosis by generating 5′-tRNA fragments, is a candidate whose expression and regulation in AD is not understood. Here, we investigated ANG expression and regulation using AD cell and animal models, postmortem human brain tissue, and transcriptomic datasets (n = 645). We found that ANG is dysregulated in AD in a sex-dependent manner, altering downstream levels of 5′-tiRNAGly-GCC. Our analysis revealed female-specific molecular subtypes, absent in males: Subtype 1 featured low ANG levels with increased inflammation and neuronal death; subtype 2 exhibited higher ANG expression and intermediate pathology; subtype 3, marked by the highest ANG levels, showed reduced inflammation, slower cognitive decline, and extended survival. These findings position ANG as a key modulator of neuroinflammation and apoptosis in AD, highlighting its potential as a treatment strategy.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

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Data

Datasets cited

Data availability

Data from the Aging, Dementia, and Traumatic Brain Injury (ADTBI) Study are publicly available at http://aging.brain-map.org/download/index and require no additional access. RNA-seq data from the ROSMAP study were retrieved from Synapse (accession: syn23446022) and are available under controlled access in accordance with human subject privacy regulations. Researchers must complete a data use agreement, required solely to protect the anonymity of ROSMAP participants. This agreement can be arranged either through Rush University Medical Center (RUMC) or through SAGE, which hosts the Synapse.org platform, where the relevant documentation is provided. All other data are included in the Supplementary information or available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

  • Publisher: n/a → Springer Nature

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 13 authors, 2 keywords, 12 MeSH terms, 3 funders, 85 references.

Cite

This paper

Jörg, M., Walz, L., Nathal, S., Kristen, M., Lietz, C., Müller, M., Nguyen, V. T. T., Ruffini, N., Winz, M.-L., Gerber, S., Endres, K., Helm, M., & Friedland, K. (2026). Sex-specific regulation of angiogenin in Alzheimer's disease. Molecular psychiatry, 31(10), 5735-5748. https://doi.org/10.1038/s41380-026-03656-7

BibTeX

@article{jorg2026sex,
author = {Jörg, Marko and Walz, Lukas and Nathal, Sebastian and Kristen, Marco and Lietz, Christine and Müller, Max and Nguyen, Vu Thu Thuy and Ruffini, Nicolas and Winz, Marie-Luise and Gerber, Susanne and Endres, Kristina and Helm, Mark and Friedland, Kristina},
title = {{Sex-specific regulation of angiogenin in Alzheimer's disease}},
journal = {Molecular psychiatry},
year = {2026},
month = jun,
volume = {31},
number = {10},
pages = {5735--5748},
publisher = {Springer Nature},
issn = {1359-4184},
doi = {10.1038/s41380-026-03656-7},
url = {https://doi.org/10.1038/s41380-026-03656-7},
pmid = {42230965},
pmcid = {PMC13569426}
}

RIS

TY - JOUR
AU - Jörg, Marko
AU - Walz, Lukas
AU - Nathal, Sebastian
AU - Kristen, Marco
AU - Lietz, Christine
AU - Müller, Max
AU - Nguyen, Vu Thu Thuy
AU - Ruffini, Nicolas
AU - Winz, Marie-Luise
AU - Gerber, Susanne
AU - Endres, Kristina
AU - Helm, Mark
AU - Friedland, Kristina
TI - Sex-specific regulation of angiogenin in Alzheimer's disease
T2 - Molecular psychiatry
J2 - Mol Psychiatry
PY - 2026
DA - 2026/06/02
VL - 31
IS - 10
SP - 5735
EP - 5748
SN - 1359-4184
PB - Springer Nature
DO - 10.1038/s41380-026-03656-7
UR - https://doi.org/10.1038/s41380-026-03656-7
LA - en
ER -

CSL-JSON

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