臨床神経学

第51回日本神経学会総会

<シンポジウム19―5>認知症研究の新しい視点
TDP-43プロテイノパチーとしてのFTLD/ALS

石原 智彦1)2), 有泉 優子1)2), 志賀 篤2), 横関 明男1), 佐藤 達哉1), 豊島 靖子3), 柿田 明美3), 高橋 均3), 西澤 正豊1), 小野寺 理2)

1)新潟大学脳研究所神経内科〔〒951―8585 新潟市中央区旭町通1番町757〕
2)同 生命科学リソース研究センター
3)同 病態神経科学部門

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)

(臨床神経, 50:1022−1024, 2010)
key words:TDP-43,前頭側頭葉変性症,筋萎縮性側索硬化症,運動ニューロン病をともなう前頭側頭葉変性症,TDP-43プロテイノパチー

(受付日:2010年5月22日)