Our novel paper “Sex-specific regulation of Angiogenin in Alzheimer’s Disease”
by Marko Jörg, Marco Kristen, Lukas Walz, Christine Lietz, Max Müller, Sebastian Nathal, Vu Thu Thuy Nguyen, Nicolas Ruffini, Marie-Luise Winz, Susanne Gerber, Kristina Endres, Mark Helm, and Kristina Friedland has been accepted for publication in Molecular Psychiatry.

We observed that angiogenin (ANG), a molecule that protects cells from stress and death, is altered in Alzheimer’s disease and shows important sex-specific effects, particularly in women. Higher ANG levels were linked to lower inflammation, slower cognitive decline, and longer survival, suggesting that ANG could be a promising target for future Alzheimer’s treatments.

Scientific abstract for our article:
tRNA modifications are critical regulators of RNA stability, decoding fidelity, and cellular stress adaptation, yet their contribution to human neurodegenerative disease remains poorly understood. Beyond their established functions in translational control, emerging evidence shows that RNA modifications influence neurogenesis, neurodevelopment, neuronal function, brain-cell differentiation, and cellular plasticity. Consequently, dysregulation of these molecular processes is increasingly recognized as a mechanistic contributor to neurodegenerative disorders. Alzheimer’s disease (AD), characterized by amyloid pathology, synaptic dysfunction, and progressive neuronal loss, has recently been linked to disturbances in RNA metabolism, suggesting that alterations in the epitranscriptome may represent an underexplored dimension of AD pathophysiology. Here, we systematically profiled the tRNA epitranscriptome across cellular and animal models of AD, as well as in human postmortem brain tissue from non-demented controls and AD patients, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Across our models, we identified a conserved yet sex-specific remodeling of the tRNA modification landscape in AD. We further developed a tRNA-centered RNA-modification score integrating nucleobase-specific modification patterns with neuropathological disease severity into a quantitative metric. Together, our findings identify the tRNA epitranscriptome as a unifying molecular sex-specific signature of AD and open new avenues toward establishing early biomarkers and diagnostic tools for Alzheimer’s disease.