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Fig. 2. Annexin A11 immunohistochemical analysis in postmortem spinal cord tissue from a SALS case with the p.D40G mutation. Annexin A11 immunohistochemical analysis in postmortem spinal cord tissue from a SALS case with the p.D40G mutation. (A) Phospho–TDP-43–positive cytoplasmic inclusion from the anterior horn of the spinal cord. (B to E) Annexin A11–positive inclusions in motor neurons of the spinal cord include skein-like structures (B) and filamentous and tubular-shaped structures (C and D). Occasional basket-like inclusions were seen in the spinal cord (E). (F) Abundant annexin A11–positive torpedo-like neuritic structures were present in the neuropil of the motor cortex (red arrows). Representative spinal cord staining for annexin A11 inclusions in a SALS case (n = 15) who is negative for ANXA11 mutations (G) and two C9ORF72 expansion–positive ALS cases (spinal cord and frontal cortex) (H and I). (J) Staining for annexin A11 inclusions was also negative in an ALS case harboring a p.D101G mutation in SOD1 (spinal cord). Similarly, frontotemporal lobar degeneration (FTLD)–TDP-43 cases (spinal cord; n = 3) (K) and Alzheimer’s disease (AD) cases (n = 3) (L) and control individuals (n = 13) (M) were also negative for staining for annexin A11 inclusions. (N and O) Double labeling of spinal cord tissue in the p.D40G SALS case for phospho–TDP-43 (green) and annexin A11 aggregates (red). (P) Costaining for ubiquitinated aggregates (red, annexin A11; green, ubiquitin) showed occasional colocalization (white arrow). Scale bars, 30 μm (A, E, G, and H), 20 μm (B and C), 15 μm (D), 50 μm (F, I, J, K, and L), 25 μm (M and N), and 50 μm (O and P). Bradley N. Smith et al., Sci Transl Med 2017;9:eaad9157 Published by AAAS
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