Donor Aware Reanalysis of Neuronal Nuclei Supports STMN2 Depletion Associated with Nuclear TDP 43 loss in FTD and ALS

Donor-aware reanalysis of FACS-isolated NeuN-positive frontal-cortex neuronal nuclei links nuclear TDP-43 loss to robust STMN2 depletion (log2FC = -1.813; FDR = 6.22e-15).

• Why it matters: Donor-to-donor variability can mask transcriptomic signals in small postmortem ALS/FTD neuronal cohorts, limiting confidence in associations with nuclear TDP-43 pathology.
• What they did: Using the GSE126542-derived matrix (62,754 genes; 12 libraries; seven donors; five matched pairs), they modeled ~ donor + nuclear_status in PyDESeq2 and contrasted TDP-43 loss versus retained.
• The result: STMN2 expression was lower in all five complete donor pairs (about 71.5% lower), while TARDBP was also reduced; UNC13A whole-gene changes were modest and model-dependent.

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