Thursday, 21 August 2003
This presentation is part of : Thursday Poster Sessions

PD-073 Modified Tau Protein in CSF for Diagnosis of Alzheimer's Disease

Toshihisa Tanaka, Hidenaga Yamamori, and Masatoshi Takeda. Division of Psychiatry and Behavioral Proteomics, Department of Post-Genomics and Diseases, Course of Advanced Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

Objective: The development of diagnostic markers for earlier and more reliable diagnosis of Alzheimer's disease (AD) is essential, particularly because therapeutic medication has been available for AD. Cerebrospinal fluid (CSF) is one of useful sources of diagnostic information. Previously we reported that the increase of oxidized tau protein, revealed by covalent binding of 2,4-dinitrophenol, in CSF of AD patients, and this method might differentiate AD from other neurological disease. The purpose of this study is to search a new biological marker more related to neurodegenerative process in AD.

Design: In the present study, CSF-tau protein with another modification, the first methionine-deletion, was examined. First, this modified tau protein was examined in the in vitro experiments that reveal the relation with acceleration of apoptosis by inhibition of anti-apoptotic protein. Second, the antibody, that recognizes the first methionine-deleted tau protein, was raised and the western blot analysis was carried out.

Materials and Methods: The peptides corresponding to the amino-terminal sequences of the normal tau and first methionine-deleted tau, were synthesized and the binding activities of them with one of anti-apoptotic proteins, were examined. And employing these peptides, the polyclonal antibody against the first methionine-deleted tau protein was raised. Then western blot analysis was carried out.

Results: The in vitro experiments revealed the binding of the peptide corresponding to the first methionine-deleted tau, but not of normal tau, with one of anti-apoptotic proteins, suggesting acceleration of apoptosis. The western blot analysis employing the antibody against the first methionine-deleted tau protein, showed increase of the immunoreactivity of CSF-tau from AD patients.

Conclusion: The results suggest that this protein modification might be involved in neurodegenerative process of AD and that this method might be useful for diagnosis of AD.

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