Complement activation in amyloid plaques in Alzheimer's disease brains does not proceed further than C3.
In Alzheimer's disease (AD) patients, the complement components Clq, C4 and C3 can be detected in different types of beta/A4 plaques, one of the hallmarks of AD. Contradictory findings on the presence of late complement components in AD brains have been reported. Nevertheless, it was suggested in recent studies that in AD brain complement activation results in complement membrane attack complex (MAC) formation and that complement activation may act as an intermediate between beta/A4 deposits and the neurotoxicity observed in AD. In the present study the presence of a number of complement components and regulatory proteins in AD temporal cortex and, for comparison, in glomerulonephritis (GN) was analysed. In GN kidneys, besides Clq, Clr, Cls and C3, the late components and the C5b-9 complex are also associated with capillary basement membrane and mesangial immune complex deposits. In AD temporal cortex Clq, C4 and C3 are co-localized with beta/A4 deposits. However, in contrast to the GN kidney, the late complement components C5, C7 and C9, as well as the C5b-9 membrane attack complex cannot be detected in beta/A4 positive plaques. The absence of the cytolytic C5b-9 complex in AD brain suggests that in AD, the complement MAC does not function as the proposed inflammatory mediator between beta/A4 deposits and the neurofibrillary changes.
Veerhuis
R
R
Department of Neuropathology, Free University Hospital, Amsterdam, The Netherlands.
van der Valk
P
P
Janssen
I
I
Zhan
S S
SS
Van Nostrand
W E
WE
Eikelenboom
P
P
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology; D002540:Cerebral Cortex / Q000737:chemistry*; D003167:Complement Activation; D003172:Complement C1 / Q000032:analysis; D003175:Complement C2 / Q000032:analysis; D003176:Complement C3 / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D003169:Complement Inactivator Proteins / Q000032:analysis*; D003165:Complement System Proteins / Q000032:analysis*; D005921:Glomerulonephritis; D006801:Humans; D007668:Kidney / Q000737:chemistry
D003172:Complement C1; D003175:Complement C2; D003176:Complement C3; D003181:Complement C4; D003169:Complement Inactivator Proteins; D003165:Complement System Proteins