Figure 5

Canonical and non-canonical pathology outside forebrain/hypothalamus in an ALS patient with forebrain/hypothalamic TDP-43 pathology, bulbar symptom onset, and survival of 29.8 months. Pathology in canonical regions, such as lower motor neurons of the hypoglossal nucleus (A), was characterized by neuronal loss, gliosis (white arrows), rarefaction of neuropil, and on TDP-43 immunostain (B), pleomorphic inclusions. Non-canonical TDP-43 pathology was seen in the deep layers of entorhinal cortex (C, D; black arrows indicate neuronal cytoplasmic inclusions in all panels), basolateral amygdala immediately overlying the temporal horn of the lateral ventricle (E, F), and hippocampal sector CA1 (G). This patient also demonstrated glial cytoplasmic inclusions (H, white arrows). All images taken at 200× (scale bar of 50 microns as shown in panel A applies to all panels).