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

• Published in: Frontiers in neuroscience 2018-01, Vol.11, p.751-751
• Main Authors: Hata, Yukiko, Ma, Ning, Yoneda, Misao, Morimoto, Satoru, Okano, Hideyuki, Murayama, Shigeo, Kawanishi, Shosuke, Kuzuhara, Shigeki, Kokubo, Yasumasa
• Format: Article
• Language: English
• Subjects: 8-Hydroxydeoxyguanosine; Alzheimer's disease; Amyotrophic lateral sclerosis; Antibodies; Basal ganglia; Central nervous system diseases; Dementia; Dementia disorders; Deoxyribonucleic acid; DNA; DNA damage; Geriatrics; Guanine; Hippocampus; Hospitals; Kii Peninsula; Kinases; Medicine; Movement disorders; Neurodegeneration; Neurodegenerative diseases; Neuropathology; Neuroscience; NF-κB protein; nitrative stress; Nitric oxide; Nitric-oxide synthase; Oxidative stress; Paraffin; Parahippocampal gyrus; parkinsonism-dementia complex; Pathogenesis; Presubiculum; Science; Subiculum; tau; Tau protein; Temporal lobe
• ISSN: 1662-4548; 1662-453X; 1662-453X
• DOI: 10.3389/fnins.2017.00751

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. 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. 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. Nitrative and oxidative stress may take priority over tau accumulation and lead to the neurodegeneration in Kii ALS/PDC.