Having spent most of his career in Alzheimer’s research on basic and mechanistic work, in recent years Iwatsubo became convinced that the time had come for a large-scale observational biomarker study in humans. He and colleagues officially launched J-ADNI in 2008. The longitudinal study closely followed the U.S. ADNI (see ARF related news story). This was neither an accident nor easy. Deliberately setting aside national pride, the Japanese scientists decided against designing and branding their own study and instead spent considerable effort to adapt the U.S. ADNI protocol to the Japanese language, even though that approach meant they would essentially repeat some data that already existed in Japanese AD research. Putting the greater good of stopping Alzheimer’s globally first, Iwatsubo’s overriding goal was to ensure J-ADNI data could be pooled with the U.S. ADNI and analyzed together for greater power. The plan worked; subsequently, presentations of pooled U.S. and J-ADNI and similar Australian data have started appearing in the literature.

Over the years, Alzforum has run numerous stories on Iwatsubo’s work and that of scientists he has mentored, particularly on the β- and γ-secretases that are crucial to clipping Aβ from its precursor protein. His research into the structure (see ARF related news story) and function (see ARF related news story) of γ-secretase components has helped researchers understand the properties of this unusual and highly complex transmembrane protease. Together with collaborators, his studies on natural (see ARF related news story) and synthetic (see ARF related news story) BACE modulators increase the chances that drugs can be found to block the rate-limiting step in Aβ production, and, indeed, drug development work in this field is active in Japan. Iwatsubo served on the Alzforum Scientific Advisory Board in 2006. In 2009 he shared the MetLife Award for his work on γ-secretase (see ARF related news story).—Tom Fagan and Gabrielle Strobel.