[A New Understanding of the Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex in the Kii Peninsula, Japan, 2026].

The distribution of amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) in the Kii Peninsula of Japan exhibits regional variations, with ALS/PDC in the Hohara focus closely resembling that in Guam and ALS in the Kozagawa focus. Recent structural analysis using cryo-electron microscopy revealed that the tau filaments in patients with ALS/PDC in Kii have a chronic traumatic encephalopathy (CTE) fold, confirming the disease's distinct pathological identity and commonality with the Guam focus. While the exact causal genes remain unidentified, research utilizing patient-derived induced pluripotent stem cells and proteomic analysis has uncovered endogenous mitochondrial dysfunction, specifically involving decreased expression of CHCHD2 and SSBP1. The presence of migrant cases further suggests that ALS/PDC is a multifactorial disorder triggered by environmental factors that influence genetic vulnerability. Although the incidence of ALS in Kozagawa and Hohara districtst has declined, new cases with PDC continue to emerge in Hohara. Identifying these modifiable environmental triggers is crucial for preventing and eradicating neurological disorders.