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Front Neurosci. 2018 Jan 22;11:751. doi: 10.3389/fnins.2017.00751. eCollection 2017.

Nitrative Stress and Tau Accumulation in Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC) in the Kii Peninsula, Japan.

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Department of Neurology, Graduate School of Medicine, Mie University, Mie, Japan.
Division of Health Science, Graduate School of Health Science, Suzuka University of Medical Science, Mie, Japan.
Department of Medical Welfare, Suzuka University of Medical Science, Mie, Japan.
Department of Oncologic Pathology, Graduate School of Medicine, Mie University, Mie, Japan.
Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
Department of Neuropathology, Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Mie, Japan.
Department of Neurology and Medicine, School of Nursing, Suzuka University of Medical Science, Mie, Japan.
Kii ALS/PDC Research Center, Graduate School of Regional Innovation studies, Mie University, Mie, Japan.


Objective: The Kii Peninsula of Japan is known to be a high incidence area of amyotrophic lateral sclerosis/parkinsonism-dementia complex (Kii ALS/PDC) with tauopathy. Nitrative stress and oxidative stress on ALS/PDC and their relationship to tau pathology were clarified. Methods: Seven patients with Kii ALS/PDC (3 males and 4 females, average age 70.7 years, 3 with ALS, 2 with ALS with dementia, and 2 with PDC) were analyzed in this study. Five patients with Alzheimer's disease and five normal aged subjects were used as controls. Immunohistochemical analysis was performed on formalin-fixed, paraffin-embedded temporal lobe sections (the hippocampal area including hippocampus, prosubiculum, subiculum, presubiculum, and parahippocampal gyri) using antibodies to detect phosphorylated tau (anti-AT-8), nitrated guanine (anti-8-NG), anti-iNOS, anti-NFκB, and oxidized guanine (anti-8-OHdG) antibodies. Results: Most hippocampal neurons of Kii ALS/PDC patients were stained with anti-8-NG, anti-iNOS, anti-NFκB, and anti-8-OHdG antibodies and some AT-8 positive neurons were co-stained with anti-8-NG antibody. The numbers of 8-NG positive neurons and 8-OHdG positive neurons were greater than AT-8 positive neurons and the number of 8-NG positive neurons was larger in patients with Kii ALS/PDC than in controls. Conclusion: Nitrative and oxidative stress may take priority over tau accumulation and lead to the neurodegeneration in Kii ALS/PDC.


Kii Peninsula; amyotrophic lateral sclerosis; nitrative stress; oxidative stress; parkinsonism-dementia complex; tau

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