Neuropathology

Staff

Prof. Iwatsubo, Takeshi, M.D.

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Overview

Our laboratory is devoted to the understanding of the molecular mechanism of neurodegeneration in the brains of patients with intractable neurodegenerative diseases, e.g. Alzheimer disease and Parkinson disease, and develop effective therapeutic strategies. Since the early histopathological discovery that Ab42 is the initially and predominantly deposited amyloid b species in senile plaque amyloid using end-specific antibodies (Neuron 1994), we have extensively incorporated biochemical and molecular/cell biological approaches. We demonstrated that mutations in presenilin genes cause familial AD by increasing the production of Ab42 (PNAS, 1997), and extended these lines of research towards the elucidation of the process of g-secretase complex formation (Nature, 2003). We have also developed a method to isolate and purify Lewy bodies from human brains (Am J Pathol, 1996) and demonstrated that a-synuclein, especially a hyperphoshorylated form, is a component of Lewy bodies (Am J Pathol, 1998, Nature Cell Biol, 2002). We also have identified a novel type of membrane-bound collagen as one of the major components of senile plaque amyloid in AD, which we named "CLAC" (EMBO J, 2002, Am J Pathol, 2004, J Biol Chem, 2005). On the clinical front, we are heading the Japanese AD Neuroimaging Initiative (J-ADNI) project, aiming at establishing standard surrogate markers for clinical trials of disease-modifying therapies for AD.

Contact

E-mail

iwatsubo@mol.f.u-tokyo.ac.jp

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