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Distribution pattern and functional state of α1-antichymotrypsin in plaques and vascular amyloid in Alzheimer's disease

An immunohistochemical study with monoclonal antibodies against native and inactivated α1-antichymotrypsin

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Summary

Monoclonal antibodies (mAbs) were raised against inactivated α1-antichymotrypsin (ACT) to study the presence and functional state of the serine protease inhibitor α1-antichymotrypsin in cerebral amyloid deposits in Alzheimer's disease. A panel of seven different mAbs was obtained; six of them were directed against neoepitopes that are expressed on ACT after interaction with proteases (inactivated ACT) and one mAb was directed against an epitope that is exposed both on native and inactivated ACT. The mAbs against neoepitopes could discriminate native ACT from complexed and inactivated ACT in vitro as shown in binding experiments in the presence of either native or inactivated ACT. With the mAbs against ACT we found that: (a) besides classical congophilic plaques, amorphous noncongophilic β/A4-positive plaques were stained; (b) amorphous and classical plaques reacted with both types of mAbs against ACT indicating that this ACT was either complexed to a protease or proteolytically inactivated; (c) vascular amyloid was not stained for ACT. The presence of ACT in amorphous and classical plaques and its absence in vascular amyloid may indicate differences in the proteolytic degradation of preamyloid into amyloid fibrils. Our study strongly suggests that ACT is biologically active in amyloid plaques from an early stage.

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Authors and Affiliations

  1. Department of Neuropathology, Academic Hospital of the Free University, Postbox 7057, NL-1007 MB, Amsterdam, The Netherlands

    J. M. Rozemuller & F. C. Stam

  2. Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands

    J. J. Abbink, A. M. Kamp & C. E. Hack

  3. Department of Psychiatry, Free University Amsterdam, Amsterdam, The Netherlands

    P. Eikelenboom

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  1. J. M. Rozemuller
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  2. J. J. Abbink
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  3. A. M. Kamp
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  4. F. C. Stam
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  5. C. E. Hack
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  6. P. Eikelenboom
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Supported by a grant of the Prevention Fund (grant no. 28-1945) and was partly supported by the Faculty of Medicine of the Free University, Amsterdam

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Rozemuller, J.M., Abbink, J.J., Kamp, A.M. et al. Distribution pattern and functional state of α1-antichymotrypsin in plaques and vascular amyloid in Alzheimer's disease. Acta Neuropathol 82, 200–207 (1991). https://doi.org/10.1007/BF00294446

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  • DOI: https://doi.org/10.1007/BF00294446

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