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. Author manuscript; available in PMC: 2024 Mar 11.
Published in final edited form as: Cell Rep. 2024 Jan 5;43(1):113636. doi: 10.1016/j.celrep.2023.113636

Figure 3. Significant disruption of proteostasis, mitochondrial dysfunction, and induction of pro-apoptotic signaling are apparent prior to overt TDP-43 aggregation.

Figure 3.

(A) Schematic of single-MN selection for laser-capture microdissection by dual detection of TDP-43 and ChAT in immediately adjacent tissue sections. Captured MNs were stratified based on TDP-43+ NCI status.

(B) Frequency of STMN2 protein detection in single MNs across TDP-43 strata.

(C) Differential protein abundances identified across TDP-43+ NCI strata (NON/MLD/MOD/SEV vs. CTL). Significant DAPs (|log2(ALS/CTL)| ≥ 1.5 ∩ p-adj < 0.05) shown in color.

(D and E) Shared or unique proteins across TDP-43 strata with significantly (D) decreased or (E) increased abundance in ALS MNs.

(F) PPI network of significant DAPs (|log2(ALS/CTL)| ≥ 1.5 ∩ p-adj < 0.05) common to all TDP-43 stages. Node color indicates fold change in protein abundance; edges denote high-confidence PPIs.