Amyotrophic lateral sclerosis and parkinsonism ‐dementia complex of the Hohara focus of the Kii Peninsula: A multiple proteinopathy?

The high incidence of amyotrophic lateral sclerosis (ALS) and parkinsonism‐dementia complex (PDC) has been previously known in the Kii Peninsula of Japan and in Guam. Recently, the accumulation of various proteins, such as tau, trans‐activation response DNA binding protein 43 kDa (TDP‐43), and alpha‐synuclein (αSyn), was reported in the brains of patients with ALS/PDC in Guam. To confirm whether similar findings are present in Kii ALS/PDC, we neuropathologically examined the brains and spinal cords of 18 patients with ALS/PDC (clinical diagnoses: eight ALS and 10 PDC) in Hohara Village, which is the eastern focus of Kii 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...

Source: Neuropathology - October 23, 2017 Category: Neurology Authors: Maya Mimuro, Mari Yoshida, Shigeki Kuzuhara, Yasumasa Kokubo Tags: Symposium: Comorbid pathologies of neurodegenerative diseases Source Type: research