前頭側頭葉変性症の概念成立の経緯と分類

History and Classification of Frontotemporal Lobar Degeneration

Ⅰ．前頭側頭葉変性症とは

　前頭側頭葉変性症（frontotemporal lobar degeneration：FTLD）とは，臨床的に特徴的な行動異常や言語機能異常がみられ，画像的には前頭葉と側頭葉を中心とした萎縮や機能低下を呈する“非Alzheimer型変性疾患の一群”を指す臨床的概念であり，臨床的，神経病理学的および遺伝学的側面においても多様であり，単一疾患ではなく種々の疾患を含む。ユビキチン陽性タウ陰性神経細胞内封入体を有する群はFTLD-U（FTLD with ubiquitin positive tau negative）と呼ばれ，2006年にこの封入体の主な構成成分がTDP-43からなることが明らかになり^1，2），FTLDは大きな研究対象となっている。FTLDと前頭側頭型認知症（frontotemporal dementia：FTD）という用語はしばしば同義的に使用されており，論文を読む際には注意が必要である。本稿ではFTDやFTLDの概念成立の経緯と分類について概説する。

Abstract

　The history and classification of frontotemporal lobar degeneration (FTLD) are reviewed in this paper.　After Pick's descriptions,there are confusions regarding the classification of the clinical syndromes and the underlying histological changes of frontotemporal lobe degeneration of the non-Alzheimer type.　In 1994,the Lund and Manchester groups proposed clinical and neuropathological criteria for the classification of frontotemporal dementia (FTD); frontal lobe degeneration type,Pick-type,and motor neuron disease (MND) type.　Ubiquitin-positive and tau-negative inclusions in the extra-motor neurons were characteristic of MND type and were first described by us.　In 1996 and 1998,Neary et al. proposed the concept of FTLD to facilitate diagnosis and provide diagnostic criteria for 3 clinical syndromes associated with FTLD,namely,FTD,progressive nonfluent aphasia,and semantic dementia.　In 2001,an international group of clinical and basic scientists reassessed the clinical and neuropathological criteria for the diagnosis of FTD and recommended revised neuropathological criteria for diagnosis.　In 2007,Cairns et al. proposed another version of the criteria for pathological diagnosis of the neurodegenerative group of diseases termed as FTLD on the basis of the recent advances in molecular genetic,biochemical,and neuropathological studies.　According to these criteria,FTLD is mainly divided into 2 groups-tauopathies and TDP-43 proteinopathies-on the basis of immunohistological methods.