臨床神経学

第49回日本神経学会総会

<シンポジウム9-1>前頭側頭型認知症(FTD)をめぐる基礎と臨床の最前線
遺伝子変異とFTD:Progranulin遺伝子をふくめて

新井 哲明1), 長谷川 成人2), 西原 真杉3), 野中 隆2), 亀谷 富由樹2), 吉田 眞理4), 橋詰 良夫4), Thomas Beach5), 森田 光哉6), 中野 今治6), 織田 辰郎7), 土谷 邦秋8), 秋山 治彦1)

1)東京都精神医学総合研究所老年期精神疾患研究チーム〔〒156-8585 東京都世田谷区上北沢2丁目1-8〕
2)同 分子神経生物学研究チーム
3)東京大学大学院農学生命科学研究科・獣医生理学教室
4)愛知医科大学加齢医科学研究所
5)Sun Health Research Institute
6)自治医科大学神経内科
7)下総精神医療センター
8)都立松沢病院検査科

Research on familial frontotemporal lobar degeneration (FTLD) has led to the discovery of disease-causing genes: microtubule-associated protein tau (MAPT), progranulin (PGRN) and valosin-containing protein (VCP). TAR DNA-binding protein of 43 kDa (TDP-43) has been identified as a major component of tau-negative ubiquitin-positive inclusions in familial and sporadic FTLD and amyotrophic lateral sclerosis (ALS), which are now referred to as TDP-43 proteinopathy. Recent findings of mutations in TDP-43 gene in familial and sporadic ALS cases confirm the pathogenetic role for TDP-43 in neurodegeneration.
TDP-43 proteinopathies have been classified into 4 pathological subtypes. Type 1 is characterized by numerous dystrophic neurites (DNs), Type 2 has numerous neuronal cytoplasmic inclusions (NCIs), Type 3 has NCIs and DNs and Type 4 has neuronal intranuclear inclusions (NIIs) and DNs. There is a close relationship between such pathological subtypes of TDP-43 proteinopathy and the immunoblot pattern of C-terminal fragments of accumulated TDP-43. These results parallel our earlier findings of differing C-terminal tau fragments in progressive supranuclear palsy and corticobasal degeneration, despite identical composition of tau isoforms. Taken together, these results suggest that elucidating the mechanism of C-terminal fragment origination may shed light on the pathogenesis of several neurodegenerative disorders involving TDP-43 proteinopathy and tauopathy.
Full Text of this Article in Japanese PDF (325K)

(臨床神経, 48:990−993, 2008)
key words:封入体, リン酸化, 断片, 神経変性, 認知症

(受付日:2008年5月17日)