Japanese contribution to the understanding of frontotemporal dementia and parkinsonism linked to chromosome 17(FTDP-17)

Since the original description of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) during the Consensus Conference held in Ann Arbor, Michigan in 1996, it has become apparent that this syndrome has worldwide distribution. More than 70 families have been described in North America, Europe, Australia and Asia. The molecular genetic studies have identified 29 mutations outside and on exon 10 of tau gene. Here, we report the progress in clinical, genetic and pathological studies of FTDP-17 in Japan. There have been 15-separetely ascertained families described in Japan. These kindreds harbor following tau mutations: exon 10, exonic mutations, N 279 K, N 296 H, P 301 L and P 301 S; exon 10 5' splice-site mutations, S 305 N (-2), 4-11, and + 12; exon 1, R 5 H mutation; exon 9, L 266 V mutation; and exon 13, R 406 W mutation. The phenotype of FTDP-17 kindreds varies significantly between families with different mutations and among the families carrying the same mutation. This variability is also seen in Japanese kindreds. Exon 10, P 301 L, + 16 and N 279 K mutations are the most common but only P 301 L and N 279 K mutations have been described so far in Japan. On the other hand, R 5 H, N 296 H, + 11, and + 12 mutations have not been identified outside of Japan. Comparison of phenotypes of Japanese and non-Japanese families with P 301 S, P 301 L and R 406 W mutations uncovers significant differences in clinical presentations. It is difficult to compare pathology of Japanese and non-Japanese families on the basis of available medical literature but no apparent differences can be seen. Autopsies demonstrate the presence of neuronal and glial tau inclusions and ballooned neurons, frequently in the distribution seen in other sporadic tauopathies. A search for the common founder in Japanese families may be successfully performed. FTDP-17 families have been identified with increasing frequency in Japan. The discovery of tau mutations and the fact that they are responsible for the disease processes in the brain lead to the major advancement of our understanding of neurodegeneration. It is hoped that future studies of these families will also lead to finding the curative treatments for the tauopathies.