Rinsho Shinkeigaku (Clinical Neurology)

The 51st Annual Meeting of the Japanese Society of Neurology

FTLD/ALS as TDP-43 proteinopathies

Tomohiko Ishihara, M.D.1)2), Yuko Ariizumi, M.D.1)2), Atsushi Shiga, M.D.2), Akio Yokoseki, M.D.1), Tatsuya Sato, M.D.1), Yasuko Toyoshima, M.D.3), Akiyoshi Kakita, M.D.3), Hitoshi Takahashi, M.D.3), Masatoyo Nishizawa, M.D.1) and Osamu Onodera, M.D.2)

1)Department of Neurology, Brain Research Institute, Niigata University
2)Department of Molecular Neuroscience, Center for Bioresource-based Researches, Brain Research Institute, Niigata University
3)Department of Pathology, Center for Bioresource-based Researches, Brain Research Institute, Niigata University

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.
Full Text of this Article in Japanese PDF (166K)

(CLINICA NEUROL, 50: 1022|1024, 2010)
key words: TDP-43, FTLD, ALS, FTLDMND, TDP-43 proteinopathy

(Received: 22-May-10)