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Introduction: In this study, we leverage proteomic techniques to identify communities of proteins underlying Alzheimer's disease (AD) risk among clinically unimpaired (CU) older adults.
Methods: We constructed a protein co-expression network using 3869 cerebrospinal fluid (CSF) proteins quantified by SomaLogic, Inc., in a cohort of participants along the AD clinical spectrum. We then replicated this network in an independent cohort of CU older adults and related these modules to clinically-relevant outcomes.
Results: We discovered modules enriched for phosphorylation and ubiquitination that were associated with abnormal amyloid status, as well as p-tau (M4: β = 2.44, p < 0.001, M7: β = 2.57, p < 0.001) and executive function performance (M4: β = -2.00, p = 0.005, M7: β = -2.39, p < 0.001).
Discussion: In leveraging CSF proteomic data from individuals spanning the clinical spectrum of AD, we highlight the importance of post-translational modifications for early cognitive and pathological changes.
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http://dx.doi.org/10.1002/alz.13576 | DOI Listing |
Commun Biol
September 2025
Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Neuronal development and function are orchestrated by a plethora of regulatory mechanisms that control the abundance, localization, interactions, and function of proteins. A key role in this regard is assumed by post-translational protein modifications (PTMs). While some PTM types, such as phosphorylation or ubiquitination, have been explored comprehensively, PTMs involving ubiquitin-like modifiers (Ubls) have remained comparably enigmatic (Ubls).
View Article and Find Full Text PDFEMBO Rep
September 2025
Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, 64287, Darmstadt, Germany.
The flexibility of the spatio-temporal genome replication program during development and disease highlights the regulatory role of plastic epigenetic mechanisms over genetic determinants. Histone post-translational modifications are broadly implicated in replication timing control, yet the specific mechanisms through which individual histone marks influence replication dynamics, particularly in heterochromatin, remain unclear. Here, we demonstrate that H3K36me3 dynamically enriches at pericentromeric heterochromatin, composed of major satellite DNA repeats, prior to replication during mid S phase in mouse embryonic stem cells.
View Article and Find Full Text PDFCell Rep Med
September 2025
Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway. Electronic address:
Accurate identification of tumor-specific markers is vital for developing chimeric antigen receptor (CAR)-based therapies. While cell surface antigens are seldom cancer-restricted, their post-translational modifications (PTMs), particularly aberrant carbohydrate structures, offer attractive alternatives. Among these, the sialyl-Tn (STn) antigen stands out for its prevalent presence in various epithelial tumors.
View Article and Find Full Text PDFDev Cell
September 2025
Division of Surgical Sciences, Department of Surgery, UC San Diego Health, 3855 Health Sciences Drive, La Jolla, CA 92037, USA. Electronic address:
In this issue of Developmental Cell, Li et al. show that ETS variant transcription factor 1 (Etv1) SUMOylation not only maintains cancer stem cells (CSCs) but also enables their communications with non-CSC cancer cells to induce tumorigenesis of non-CSCs. The finding reveals a new function of CSCs in driving aggressive tumorigenesis that is SUMOylation dependent.
View Article and Find Full Text PDFTree Physiol
September 2025
Pollen Biotechnology of Crop Plants Group, Margarita Salas Center of Biological Research, CIB-CSIC, Ramiro de Maeztu 9, 28040, Madrid, Spain.
Somatic embryogenesis (SE) is an in vitro mass propagation system widely employed in plant breeding programs. However, its efficiency in many forest species remains limited due to their recalcitrance. SE relies on the induction of somatic cell reprogramming into embryogenic pathways, a process influenced by transcriptomic changes regulated, among other factors, by epigenetic modifications such as DNA methylation, histone methylation, and histone acetylation.
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