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• W2765183304 abstract "The high incidence of amyotrophic lateral sclerosis ( ALS ) and parkinsonism‐dementia complex ( PDC ) has been previously known in the K ii P eninsula of J apan and in G uam. Recently, the accumulation of various proteins, such as tau, trans‐activation response DNA binding protein 43 kDa (T DP ‐43), and alpha‐synuclein (α S yn), was reported in the brains of patients with ALS / PDC in G uam. To confirm whether similar findings are present in K ii ALS / PDC , we neuropathologically examined the brains and spinal cords of 18 patients with ALS / PDC (clinical diagnoses: eight ALS and 10 PDC ) in H ohara V illage, which is the eastern focus of K ii ALS . The average age at death was 71.6 years, and 16 patients (88.9%) had a family history of ALS / PDC . Autopsy specimens were immunohistochemically examined with antibodies against four major proteins. Neurofibrillary tangles, including ghost tangles, and tau‐positive astrocytes were distributed widely in all of the brains examined, and TDP ‐43‐positive neuronal cytoplasmic inclusions were observed mainly in the limbic system. Synuclein pathology was present in 14 patients (77.8%). These patients were classified into three pathological subtypes according to the most prominent proteinopathy: the tauopathy‐dominant type, the TDP ‐43 proteinopathy‐dominant type, and the synucleinopathy‐dominant type. Five patients with severe tau deposition showed clinical features of atypical parkinsonism and dementia with or without motor neuron disease. Eight patients were predominated by phosphorylated TDP ‐43 inclusions and clinically showed ALS , and five patients were predominated by synuclein pathology and clinically showed signs of PDC . Based on the common characteristic tau pathology, three subtypes seemed to be pathologically continuous on a spectrum of a single disease. Thus, we conclude that ALS / PDC in the H ohara focus of the K ii P eninsula is a single disease characterized neuropathologically by a multiple proteinopathy, even though the clinical manifestations of the three subtypes differed from each other. It remains unclear whether the coexistence of the three proteinopathies was incidental or pathogenetically related." @default.
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• W2765183304 date "2017-10-23" @default.
• W2765183304 modified "2023-10-18" @default.
• W2765183304 title "Amyotrophic lateral sclerosis and parkinsonism-dementia complex of the Hohara focus of the Kii Peninsula: A multiple proteinopathy?" @default.
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• W2765183304 doi "https://doi.org/10.1111/neup.12434" @default.
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