title: Concomitant accumulation of α-synuclein and TDP-43 in a patient with corticobasal degeneration.
abstract: Pathological changes in corticobasal degeneration (CBD) consist of abnormal deposition of the microtubule-associated protein tau. However, the simultaneous accumulation of different misfolded proteins in the brain can be observed in many neurodegenerative diseases with significantly longer disease durations. We encountered a patient with CBD who survived for an extremely long period (18 years) after the diagnosis. We performed an autopsy to elucidate the effect of the longer survival on the pathology of CBD. We observed abnormal aggregation of trans-activating response region DNA-binding protein of 43 kDa (TDP-43) and α-synuclein, as well as phosphorylated tau, in neurons of broader regions of the brain, beyond the amygdala and other limbic areas. We found that phosphorylated tau, α-synuclein, and TDP-43 partially co-existed in the same cellular aggregates. The triple pathologic changes might be related to the longer survival of the patient compared with the typical clinical course of patients with CBD. Further investigations are required to support the hypothesis that tauopathy, synucleinopathy, and TDP-43 proteinopathy might share common pathogenic mechanisms in terms of cross-seeding of the pathologic proteins.
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan, y-stsh@kumamoto-u.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Naomi
authors.initials: N
authors.lastname: Sakashita
authors.forename: Taro
authors.initials: T
authors.lastname: Yamashita
authors.forename: Nozomu
authors.initials: N
authors.lastname: Tawara
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Tasaki
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kawakami
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komohara
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Masashi
authors.initials: M
authors.lastname: Kamikawa
authors.forename: Takenobu
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Hirano
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Maeda
authors.forename: Masato
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
mesh_terms: D000368:Aged; D002540:Cerebral Cortex / Q000737:chemistry / Q000473:pathology; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000378:metabolism; D017809:Fatal Outcome; D006801:Humans; D008297:Male; D019636:Neurodegenerative Diseases / Q000175:diagnosis* / Q000378:metabolism; D051844:alpha-Synuclein / Q000032:analysis* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C000598624:TARDBP protein, human; D051844:alpha-Synuclein