|Masahito Yamada, MD, PhD
Professor & Chair
Welcome to our homepage of the Department of Neurology and Neurobiology of Aging at Kanazawa University Graduate School of Medical Sciences / Neurological Clinic, Kanazawa University Hospital.
Our mission is to overcome neurological disorders through high-level clinical, research, and educational activities. The research subjects include:
1.Amyloid, dementia, and brain aging. Clinical and experimental studies are ongoing, particularly focusing on protein aggregation, to develop preventives/therapeutics of Alzheimer's disease (AD), cerebral amyloid angiopathy (CAA), dementia with Lewy bodies (DLB)/Parkinson's disease, and other aging-related disorders.
2.Prion diseases. Our laboratory is a center of clinical research on prion diseases in Japan (see Atarashi et al. Nat Med 2011, Nozaki et al. Brain 2010, Yamada et al. Lancet 2006, etc.)
3.Neuroimmunology. Our research has focused on myasthenia gravis and other neuroimmunological disorders.
4.Neuroimaging. AD, DLB, CAA, and other aging-related disorders have been studied with PET (FDG/amyloid), MIBG myocardial scintigraphy, and other imaging modalities.
5.Community-based study on brain aging and dementia ("Nakajima Project"). The project is ongoing in the town of Nakajima, Nanao city, Ishikawa prefecture, Japan, in order to develop methods of early detection and prevention of dementia/cognitive impairment in the aging population.
I greatly appreciate collaboration with many institutions all over the world. I encourage young people to join us and to extend clinical and research activities to overcome neurological disorders.
The Amyloid Research Group has started work since 2000, when Prof. Masahito Yamada moved into Kanazawa University. First, we engaged in biophysical research of amyloid β-protein (Aβ) aggregation with Prof. Hironobu Naiki (Fukui University). Previously, we found that some organic compounds with antioxidative motif, such as curcumin, wine-related polyphenols and nicotine inhibit both Aβ and α-synuclein (αS) aggregations, as well as destabilize preformed fibrils of Aβ and αS in vitro. Moreover, the cerebrospinal fluid (CSF) from non-Alzheimer disease (AD) patients inhibited the Aβ aggregation more strongly than that from AD patients although the CSF obtained from both groups inhibited Aβ aggregation. From 2007, we developed our research more deeply with Professor David B Teplow (UCLA). We are mainly focusing on the biological and structural approach of Aβ and αS oligomers. From 2007-now, we found that phenolic compounds inhibit Aβ oligomerization and decreased cellular and synaptic toxicities with Prof. Giulio M Pasinetti (Mount Sinai Hospital), Prof. Hisao Nishijo (Toyama University), Dr. Akihiko Takashima, Dr. Yuji Yoshiike (National Center for Geriatrics and Gerontology). Moreover, we elucidated the binding site of phenolic compounds with Aβ using NMR with Prof. Michael G Zagorski (Case Western Reserve University). We also found that melatonin blocks all steps of αS aggregation including protofibril formation, oligomerization, and secondary structure transitions. Importantly, we found that melatonin decreased αS-induced cytotoxicity with Prof. Hideki Mochizuki (Osaka University).
Prion disease research
We are investigating clinical and epidemiological studies about prion diseases to prevent developing prion diseases. At the present, we have reported some valuable articles, such as clinical diagnosis of MM2 type sporadic CJD (Neurology 2005), the first case of variant CJD (Lancet 2006), clinical features and diagnosis of dura mater graft associated CJD (Neurology), medical procedures and risk of sCJD (Emerg Infect Dis 2009), and prospective 10-year surveillance of human prion diseases in Japan (Brain 2010).
The Neuroimmunology Research Group has started work since 1982, when Dr Masaharu Takamori moved into department of neurology, Kanazawa University. Dr Takamori retired Kanazawa University in 1999, our group has studied autoimmunity in nerve and muscle diseases. The core scientists are Dr Hiroaki Yoshikawa, Dr Kazuo Iwasa, Dr Takahiro Maruta, Dr Kazuya Takahashi and Dr Daisuke Noto. We aim to elucidate myasthenia gravis, multiple sclerosis and other neuroimmunological diseases by using in basic and clinical science methods. In MG research, we have researched about functions of MG antibodies and muscle cell homeostasis. In MS research, we have studied about microglia functions. We are progressing the advanced studies for discovering more effective MG and MS treatments.
The neuroimaging research group investigates the role of brain imaging by PET and MRI in early and objective assessment of Alzheimer's disease (AD) and other forms of neurodegenerative diseases. This study was performed as a part of the Ishikawa Brain Imaging Study (IBIS) (initiated in 2002), collaborated with the Medical and Pharmacological Research Center Foundation (Dr. Matsunari). In addition, the office of the multi-center study "Diagnostic role of cardiac sympathetic function assessment in Dementia with Lewy bodies and Alzheimer's disease" has been set in our department. We also take part in the multisite, longitudinal clinical and biomarker study of AD "Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI)".
A population-based prospective study of the early detection of dementia and the effectiveness of intervention for dementia was established in 2006 in the town of Nakajima in the Nanao distinct of Ishikawa Prefecture, Japan. Since 2006, all residents of Nakajima town aged 60 and older can attend annual check-up services of the health status and brain function. The examination was performed in the public hall of the town or at home.