FTDP-17の神経病理

Neuropathology of FTDP-17

　FTDP-17はタウ蛋白遺伝子の変異を疾患原因とする脳変性疾患であり，前頭側頭型痴呆，パーキンソン症候群を主とした錐体外路徴候，常染色体優性の遺伝様式が臨床的特徴である。本疾患に特異的なタウ蛋白遺伝子変異はexon 1と9以下13までの各exon，およびexon 10に継ぐintron部位（IVS 10）に計30種類以上が報告されている。病理形態的には，IVS 10と一部のexon 10における変異型（N279K等）においてPSP/CBDに類似した深部灰白質病変が優位となり，neuronとglia双方に原線維変化を伴う傾向がみられ，それ以外の変異では神経原線維変化が優位な前頭側頭型痴呆を呈する傾向が知られている。だが，N279K・S305N・IVS 10＋16・R406Wでは，同一変異例の中でも病理所見に一定の多様性が認められ，直接的に遺伝子異常に規定されない他の要因が表現型に関与することが示唆される。

　Frontotemporal dementia and parkinsonism linked to chromosome 17（FTDP-17）is a neurodegenerative disorder caused by mutations of the tau protein gene. This disorder is characterized clinically by frontotemporal dementia, extrapyramidal signs such as Parkinson's syndrome, and an inheritance of autosomal dominant fashion. The tau gene mutations specific to this disorder are located in the exon 1, in five exons from 9 to 13, and in the intron following exon 10（IVS 10）. Heretofore, more than 30 different mutations have been reported.

　Neuropathological studies have revealed a tendency for mutations in IVS 10, in addition to part of those in the exon 10（ex. N279K）, to exhibit deep gray matter lesions resembling those of PSP/CBD and marked fibrillary changes both in neurons and glias, whereas for other tau gene mutations to show frontotemporal degeneration with neurofibrillary change dominance. However, certain mutations, for instances N279K, S305N, IVS 10＋16, and R406W, exhibit considerable variety of neuropathological features among patients with the same mutation. Therefore, certain factors, which are not directly regulated by the mutations, might also influence the phenotypes of FTDP-17.