Complement activation in human prion disease

• Published in: Neurobiology of disease Vol. 15; no. 1; pp. 21 - 28
• Main Authors: Kovacs, Gabor G, Gasque, Philippe, Ströbel, Thomas, Lindeck-Pozza, Elisabeth, Strohschneider, Michaela, Ironside, James W, Budka, Herbert, Guentchev, Marin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2004; Elsevier
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies - immunology; Antibody Specificity; Brain - immunology; Brain - physiopathology; Complement; Complement C1q - immunology; Complement C3b - immunology; Complement Membrane Attack Complex - immunology; Complement System Proteins - immunology; Creutzfeldt–Jakob disease; Female; Humans; Immunity, Innate - immunology; Immunohistochemistry; Male; Membrane attack complex; Middle Aged; Neurons - immunology; Prion disease; Prion Diseases - immunology; PrPSc Proteins - immunology; Membrane attack complex; Prion disease; Complement; Creutzfeldt–Jakob disease
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2003.09.010

The central event in the neuropathological process of prion diseases (PrD) is the accumulation of abnormal prion protein accompanied by severe neuronal loss. Despite the infectious nature of these diseases, no prominent immune response has been detected yet. However, recent studies have shown that complement, a component of the innate immune system, is involved in the early pathogenesis of experimental prion infection. Here we demonstrate, in the diseased human brains, the presence of active compounds of the complement system, like C1q and C3b, in extracellular disease-associated prion protein deposits and the membrane attack complex in neurons. The neuronal localization of the membrane attack complex correlates well with the severity of disease-specific pathology and TUNEL labeling of neurons, irrespective of genotype or molecular phenotype of human prion diseases.