Distribution pattern and functional state of alpha 1-antichymotrypsin in plaques and vascular amyloid in Alzheimer's disease. A immunohistochemical study with monoclonal antibodies against native and inactivated alpha 1-antichymotrypsin.
Monoclonal antibodies (mAbs) were raised against inactivated alpha 1-antichymotrypsin (ACT) to study the presence and functional state of the serine protease inhibitor alpha 1-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 beta/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.
Department of Neuropathology, Academic Hospital of Free University, Amsterdam, The Netherlands.
J M
JM
Rozemuller
J J
JJ
Abbink
A M
AM
Kamp
F C
FC
Stam
C E
CE
Hack
P
P
Eikelenboom
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D000682:Amyloid / Q000032:analysis*; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001921:Brain / Q000473:pathology*; D010450:Endopeptidases / Q000032:analysis / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000473:pathology; D011480:Protease Inhibitors / Q000032:analysis / Q000276:immunology; D011863:Radioimmunoassay; D000514:alpha 1-Antichymotrypsin / Q000032:analysis* / Q000276:immunology / Q000378:metabolism
D000682:Amyloid; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D011480:Protease Inhibitors; D000514:alpha 1-Antichymotrypsin; D010450:Endopeptidases