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Angiogenin (ANG), a stress-responsive ribonuclease that inhibits apoptosis by generating 5\u2032-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                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009645). We found that ANG is dysregulated in AD in a sex-dependent manner, altering downstream levels of 5\u2032-tiRNA\n                    <jats:sup>Gly-GCC<\/jats:sup>\n                    . 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.\n                  <\/jats:p>","DOI":"10.1038\/s41380-026-03656-7","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:46:56Z","timestamp":1780411616000},"page":"5735-5748","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex-specific regulation of angiogenin in Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5799-1172","authenticated-orcid":false,"given":"Marko","family":"J\u00f6rg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Walz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Nathal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Kristen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Lietz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7673-1559","authenticated-orcid":false,"given":"Max","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vu Thu Thuy","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3342-6756","authenticated-orcid":false,"given":"Nicolas","family":"Ruffini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0740-8618","authenticated-orcid":false,"given":"Marie-Luise","family":"Winz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9513-0729","authenticated-orcid":false,"given":"Susanne","family":"Gerber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1099-8287","authenticated-orcid":false,"given":"Kristina","family":"Endres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Helm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8603-5957","authenticated-orcid":false,"given":"Kristina","family":"Friedland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"3656_CR1","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1007\/s12035-012-8300-y","volume":"46","author":"K Leuner","year":"2012","unstructured":"Leuner K, Schulz K, Sch\u00fctt T, Pantel J, Prvulovic D, Rhein V, et al. 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The Religious Orders Study and Rush Memory and Aging Project (ROSMAP) were approved by the Institutional Review Board of Rush University Medical Center (ROS IRB# L91020181, MAP IRB# L86121802, RADC Repository IRB# L99032481) and conducted in accordance with the Declaration of Helsinki. All participants provided informed consent and signed an Anatomic Gift Act and RADC Repository consent allowing data and biospecimens to be repurposed. The Adult Changes in Thought (ACT) study was approved by the Institutional Review Board of Kaiser Permanente Washington Health Research Institute. Participants provided informed consent at enrollment and renewed consent at each study visit, including permission for sharing de-identified data with external investigators. Human postmortem brain samples from the Netherlands Brain Bank (NBB; project number 1341) were obtained in accordance with the ethical and legal guidelines of the NBB. All procedures were approved by the Independent Review Board Ethics Committee of the VU University Medical Center (Amsterdam, The Netherlands; Medisch Ethische Toetsingscommissie, METc #2009\/148). All participants provided informed consent for postmortem brain autopsy and the use of brain tissue and clinical data for research purposes. All animal procedures were conducted in accordance with the European Communities Council Directive (2010\/63\/EU), the ARRIVE guidelines and the local animal ethics committee guidelines (Landesuntersuchungsamt Rheinland-Pfalz, LUA).","order":2,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Ethics"}}]}}