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Different immunoreactivities of the microtubule-binding region of tau and its molecular basis in brains from patients with Alzheimer's disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration

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Abstract

The microtubule-associated protein tau accumulates as cytoplasmic inclusions in Alzheimer's disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We investigated the immunoreactivity of tau-positive structures using a panel of antibodies to epitopes spanning the entire length of the tau molecule. In ethanol-fixed brain tissues, most antibodies to the microtubule-binding domain (MBD) required formic acid (FA) treatment to stain tau inclusions in PSP and CBD. This is in contrast with the intense labeling of neurofibrillary tangles in AD without FA treatment. Pick bodies (PiB) in PiD showed an intermediate pattern with respect to the immunoreactivity of the MBD because accumulated tau in PiB mostly lacks the insertion of exon 10, and the proportion of tau phosphorylated at Ser262 is smaller than in other abnormal tau structures. Such immunohistochemical profiles appeared to correlate with the occurrence of the smeared tau on immunoblot analysis of brain homogenate. The smeared tau was more abundant in AD and PiD than in PSP and CBD. Since the smeared tau was N-terminally truncated and was characteristic of advanced forms of modified tau, these findings suggest that tau accumulated in AD and PiD was processed more markedly than that in PSP and CBD. The MBD of tau may be masked in the presence of the intact N terminus and require FA treatment for antibody recognition in tissue sections. Advanced modification may expose the MBD in brain tissues of AD and PiD. It is suggested that the processing of abnormally accumulated tau characterizes the pathophysiology of each tauopathy.

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Acknowledgements

This study was supported by a grant-in-aid for encouragement of young scientists from the Ministry of Education, Science, Sports and Culture of Japan (12780576) and the Welfide Medicinal Research Foundation. We thank Dr. P. Davies (Albert Einstein College of Medicine, USA) for Alz-50, MC-1, TG3 and PHF-1, Dr. H. Mori (Osaka City University Medical School, Japan) for TF11, and Elan Pharmaceuticals for 12E8. We also thank Drs. T. Beach and J. Rogers for providing brain tissues.

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Authors and Affiliations

  1. Department of Psychogeriatrics, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, 156-8585, Tokyo, Japan

    Tetsuaki Arai, Kenji Ikeda & Haruhiko Akiyama

  2. Tokyo Metropolitan Matsuzawa Hospital, 2-1-1 Kamikitazawa, Setagaya-ku, , 156-0057, Tokyo, Japan

    Kuniaki Tsuchiya & Shuji Iritani

  3. Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida-shi, , 194-8511, Tokyo, Japan

    Koichi Ishiguro

  4. Division of Pathology, Kanagawa Rehabilitation Center, Nanasawa 516, Atsugi, 243-01, Kanagawa, Japan

    Saburo Yagishita

  5. Department of Neuropsychiatry, National Shimofusa Mental Hospital, 266-0007, Chiba, Japan

    Tatsuro Oda

  6. Department of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, 236-0004, Yokohama, Japan

    Toshinari Odawara & Eizo Iseki

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  1. Tetsuaki Arai
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  2. Kenji Ikeda
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  3. Haruhiko Akiyama
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  9. Toshinari Odawara
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Correspondence to Tetsuaki Arai.

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Arai, T., Ikeda, K., Akiyama, H. et al. Different immunoreactivities of the microtubule-binding region of tau and its molecular basis in brains from patients with Alzheimer's disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration. Acta Neuropathol 105, 489–498 (2003). https://doi.org/10.1007/s00401-003-0671-8

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  • DOI: https://doi.org/10.1007/s00401-003-0671-8

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