Neuroanatomic distribution of FUS pathology in aFTLD-U and late-onset BIBD. (A) FUS pathology grades for brain regions were averaged for aFTLD-U versus BIBD and forebrain regions were plotted from anterior brain regions (mid-frontal and orbitofrontal cortex) to posterior brain regions (visual cortex). aFTLD-U scores are shown with black squares while BIBD scores are shown with open circles. (B) Average FUS pathology grades for brainstem and spinal cord regions were plotted from rostral to caudal. Cerebellum scores represent grades from the dentate nucleus only, and does not reflect the absence of pathology in the cerebellar folia. aFTLD-U scores are shown with black squares while BIBD scores are shown with open circles. (C) Average FUS pathology grades for various groups of brain regions are shown for aFTLD-U (black bars) and BIBD (clear bars). Limbic regions included amygdala, hippocampus, parahippocampal gyrus, orbitofrontal cortex and cingulate gyrus. Nonisocerebral cortex regions included parahippocampal gyrus, cingulate gyrus and orbitofrontal cortex. Neocortical regions included mid-frontal cortex, superior and inferior temporal cortex, angular gyrus, motor cortex, sensory cortex and visual cortex. Extrapyramidal motor regions included basal ganglia, thalamus, midbrain including substantia nigra, pons including locus ceruleus, dentate nucleus of the cerebellum and the medullary inferior olive nucleus. Motor regions included the motor cortex and the ventral spinal cord grey matter. (D) The hypothetical spread of FUS pathology is shown based on the topography of FUS inclusions which emphasizes the more widespread involvement of the brain in aFTLD-U with a predilection for anterior forebrain, cerebral cortex and limbic brain regions compared to the pattern of FUS pathology in BIBD which involves primarily pyramidal and extrapyramidal motor regions with relative sparing of other brain regions. Although speculative, the topographic distribution of FUS pathology suggests that aFTLD-U and late-onset BIBD exhibit differences in the spread of FUS pathology.