EV-based biomarkers for Alzheimer’s disease

Hokkaido University
Institute for the Promotion of Business-Regional Collaboration/Faculty of Advanced Life Science
Associate professor

Dr. Kohei YUYAMA

Alterations in molecules contained within extracellular vesicles (EV) have been reported in the pathogenesis and progression of Alzheimer's Disease (AD) and are considered potential biomarker candidates for detecting the pathology. To analyze the dynamics of EV in vivo, we have developed a novel immuno-digital invasive cleavage assay (idICA) method, which digitally detects EVs with specific surface molecules using a micro-well device. Using this method to measure amyloid-beta (Abeta)-bound glycolipid GM1-containing EV in the blood of AD model mice, we confirmed that the concentration of Abeta-GM1-EV increases with amyloid accumulation. This technique is useful for the diagnosis of AD and the determination of therapeutic efficacy and may contribute to the development of new EV-based biomarkers.

Tokyo Metropolitan Institute of Medical Science
Department of Brain and Neurosciences
Head

Mr. Masato HASEGAWA

Accumulation of pathological proteins (tau, alpha-synuclein, TDP-43, etc.) in the brain is a hallmark of major neurodegenerative diseases. Genetic studies suggest that aggregates of these proteins have some toxicity and are responsible for neurodegeneration. Importantly, the distribution and spread of lesions are closely associated with the symptoms and progression of these diseases. To explain the pathogenesis and progression of these disease, "prion-like propagation" has been proposed and verified, in which abnormal proteins act as seeds to convert normal proteins into abnormal proteins. The structures of filamentous proteins that accumulate in these brains have also been elucidated by cryo-electron microscopy, supporting this idea. It has been proposed that neurodegenerative diseases can be classified according to the folding structures, and diagnostic and therapeutic agents targeting prion-like propagation are being developed.

International University of Health and Welfare

Mr. Hiroaki SHIMOKAWA

1979 Graduated from Kyushu University School of Medicine
1985 Mayo Clinic, Research Fellow
1990 Physician in Chief, Cardiology, Iizuka Hospital
1991 Assistant professor, Department of Cardiology, Kyushu University Hospital
1995 Associate Professor, Department of Cardiology, Kyushu University
2005 Professor, Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
2013 Director, Clinical Research, innovation and Education Center, Tohoku University Hospital (Concurrent post)
2020 Vice Dean, Graduate School, International University of Health and Welfare

Specialty: Cardiology
Research area: Ischemic heart disease, Heart failure, Vascular biology, Advanced medical development

Focusing on the self-healing ability of sound waves, I have been developing advanced therapies. I have found that certain conditions of low-intensity pulsed ultrasound (LIPUS) exert several regenerative effects including angiogenesis. Interestingly, LIPUS induces angiogenesis in ischemic tissue, lymph-angiogenesis in edematous tissue, and neurogenesis in tissue with neuronal damage. First, I demonstrated that the LIPUS therapy ameliorates myocardial ischemia in a pig model and patients with angina pectoris. Next, I was able to demonstrate that the LIUPS therapy is effective in two different mouse models of dementia (Alzheimer’s disease (AD) and vascular dementia). Then, I performed a pilot trial with patients with early AD, which showed the safety and strongly suggested the efficacy of the LIPUS therapy. Based on these encouraging results, I am now performing a final pivotal trial for early AD in Japan.