Neuropathology of Speech Network Distinguishes Bulbar From Nonbulbar Amyotrophic Lateral Sclerosis.
Bulbar amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative subtype affecting speech and swallowing motor functions as well as associated with the burden of cognitive deficits. The neuroanatomical underpinnings of bulbar ALS are not well understood. The aim of this study was to compare neuropathology of the speech network (SpN) between 3 cases of bulbar-onset ALS (bALS), 3 cases of spinal-onset ALS (sALS) with antemortem bulbar ALS (sALSwB) against 3 sALS without antemortem bulbar ALS (sALSnoB) and 3 controls. Regional distribution and severity of neuronal loss, TDP-43 (transactive response DNA-binding protein of 43 kDa), and tau proteinopathy were examined. All 3 bALS cases showed marked neuronal loss and severe proteinopathy across most SpN regions; sALSwB cases showed no neuronal loss but mild and variable TDP-43 pathology in focal regions; sALSnoB cases demonstrated an absence of pathology. Two bALS cases had coexisting tauopathy in SpN regions, which was not noted in any sALS cases. The findings suggested that bALS may have a distinct neuropathological signature characterized by marked neuronal loss and polypathology in the SpN. Milder TDP-43 pathology in the SpN for sALSwB cases suggested a link between severity of bulbar ALS and SpN damage. Findings support a clinicopathologic link between bulbar symptoms and pathology in the SpN.
['Shellikeri|Sanjana|S|', 'Keith|Julia|J|', 'Black|Sandra E|SE|', 'Zinman|Lorne|L|', 'Yunusova|Yana|Y|']
D000368:Aged D000690:Amyotrophic Lateral Sclerosis D002540:Cerebral Cortex D004268:DNA-Binding Proteins D005260:Female D005911:Gliosis D006801:Humans D002479:Inclusion Bodies D008297:Male D008875:Middle Aged D009434:Neural Pathways D009474:Neurons D013060:Speech D016875:tau Proteins
Neuropathology Speech network Bulbar Amyotrophic lateral sclerosis (ALS) Frontotemporal lobar degeneration (FTLD) Immunohistochemistry