Fig. 6.

Electron microscopy of three ALS muscle samples (study samples ALS23, ALS34, and ALS43). For each muscle sample, a region-of-interest was dissected out of the FFPE block in a region with maximal pTDP-43 and p62 inclusion pathology and subsequently processed for electron microscopy using a protocol for FFPE specimens (see Methods). Filamentous material (black arrows in all three rows) is present in these foci, entirely within myofibers and sharply demarcated from degenerating myofibrils (white arrow, middle row, left-most panel). Basement membrane (black asterisk, middle row, left panel) and nuclear clumps (white arrow, top row, left panel) are also identified, despite the degenerated nature of the specimen. The filamentous material identified predominantly measures between 10 and 20 nm in thickness (right panels of top and middle rows, which are enlargements of the middle panels in their respective rows). In the bottom row, the middle and right-most panels show accumulation of this material adjacent to invaginations of the cell membrane at an apparent neuromuscular junction (white asterisks). Scale bar and magnifications are shown for each panel