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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.

Author information

1
Department of Neurology, Graduate School of Medicine, Mie University, Mie, Japan.
2
Division of Health Science, Graduate School of Health Science, Suzuka University of Medical Science, Mie, Japan.
3
Department of Medical Welfare, Suzuka University of Medical Science, Mie, Japan.
4
Department of Oncologic Pathology, Graduate School of Medicine, Mie University, Mie, Japan.
5
Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
6
Department of Neuropathology, Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
7
Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Mie, Japan.
8
Department of Neurology and Medicine, School of Nursing, Suzuka University of Medical Science, Mie, Japan.
9
Kii ALS/PDC Research Center, Graduate School of Regional Innovation studies, Mie University, Mie, Japan.

Abstract

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.

KEYWORDS:

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

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