ROLE OF COMPLEMENT IN THE ETIOLOGY OF PICKS-DISEASE

Complement in the postmortem brains of 15 cases of Pick's disease has been widely analyzed immunohistochemically and, in 2 cases, by immunoe lectron microscopy. Astrocytes and the Pick bodies and cytoplasm of ba llooned neurons were immunoreactive with antibodies to classical pathw ay components C1, C1q, C4, C2 and C3 and the terminal complex componen ts C5, C6 and C8. In almost all cases, no immunostaining was obtained with antibodies against C9 and neoepitopes in the membrane attack comp lex (MAC), the complement complex responsible for cytotoxicity. Howeve r, unequivocal staining with antibodies to two soluble complement regu latory proteins, S-protein and clusterin, and to the membrane compleme nt inhibitor CD59 was found, although three other membrane inhibitors, CR1(CD35), DAF (CD55), and MCP (CD46), were not detected. The complem ent immunoreactivity of astrocytes and neurons could be the result of complement biosynthesis or attack. Complement attack will be restricte d by the expressed regulatory proteins. However, neurons may be the vi ctims of attack since they show pathological change. The internalizati on of complement-attacked membrane, perhaps involving the genesis of P ick bodies and ballooning, may explain the intracellular immunolocaliz ation of complement in damaged neurons. Immunoglobulins, as a possible source of complement activation, were observed in only two cases, lea ving unresolved the trigger for complement activation in the other cas es.