title: [FTLD/ALS as TDP-43 proteinopathies].
abstract: Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) often coexist in the same patients: FTLD/MND. However, it is unclear whether FTLD/MND can be distinguished from ALS or FTLD. TAR DNA binding protein 43 KDa (TDP-43) has been identified as the major component of the ubiquitin-positive inclusion bodies in ALS, FTLD, and FTLD/MND. On the basis of this finding, a new concept of neurodegenerative disorders, namely TDP-43 proteinopathy, has been proposed for these disorders. In ALS, more than 30 mutations of the TDP-43 gene have been identified. The clinical features and neuropathological findings of ALS with TDP-43 mutation are identical to those of sporadic ALS. Therefore, TDP-43 plays a primary role in the pathogenesis of ALS. In contrast, only few patients with FTLD phenotype have TDP-43 mutations. Therefore, we have speculated that TDP-43 does not play a primary role in the pathogenesis of FTLD. The analysis of distribution of TDP-43 inclusion bodies in ALS patients revealed that ALS has two subtypes: (1) limited in the motor neuron system and (2) extended into the frontotemporal lobe. Additionally, causative genes of familial FTLD/MND have not been mapped to TDP-43. These results suggest that FTLD/MND is a disease distinct from FTLD and ALS.
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ishihara
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ariizumi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiga
authors.forename: Akio
authors.initials: A
authors.lastname: Yokoseki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sato
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Toyoshima
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Masatoyo
authors.initials: M
authors.lastname: Nishizawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Onodera
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000145:classification / Q000473:pathology / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D057174:Frontotemporal Lobar Degeneration / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D009154:Mutation; D057177:TDP-43 Proteinopathies / Q000473:pathology / Q000503:physiopathology
chemical_list: D004268:DNA-Binding Proteins