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Integrative synaptosome multi-omics reveals disrupted synapse organization and localized cryptic transcripts in C9ORF72-Frontotemporal Dementia

A. Spillman E. Alsop L. M. Gittings K. Garcia-Mansfield I. Piras A. Bonfitto Melissa N. Martinez Ritin Sharma Kim R. Preller M. Huentelman P. Pirrotte K. V. Van Keuren-Jensen Rita Sattler

Jul 2026 · bioRxiv · 0 citations · 47 references

Medicine Biology

TL;DR

Combined multi-omic profiling of synaptosomes enriched from postmortem frontal cortex and patient-derived induced pluripotent stem cell (iPSC)-derived cortical neurons defines convergent molecular pathways underlying synapse vulnerability in both C9-FTD model systems and identifies synaptic localization of CE-containing transcripts as a previously unrecognized feature of TDP-43 proteinopathy.

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