Complement regulators C1 inhibitor and CD59 do not significantly inhibit complement activation in Alzheimer disease.
Proteins characteristic of activated complement are associated with Alzheimer disease (AD) lesions. The classical complement pathway can be activated only when the influence of such endogenous regulators as C1-inhibitor (C1-inh) and CD59 are overcome. We used the techniques of reverse transcriptase-polymerase chain reaction and Western blotting to assess the mRNA and protein levels of C1-inh and CD59 in AD and control brains in comparison with levels of the complement components with which they interact. The inhibitors were only slightly upregulated and then only in heavily affected areas of AD brain such as the entorhinal cortex, hippocampus, midtemporal gyrus and midfrontal gyrus. The ratio of AD to control mRNAs in these four areas was 1.17 for C1-inh and 1.12 for CD59, compared to 3.06 for C1r, 2.67 for C1s, 2.35 for C5, 2.56 for C6, 2.42 for C7, 5. 08 for C8 and 16.3 for C9. Peripheral organ expression of C1-inh and CD59 mRNAs was no different in AD than controls but was slightly upregulated in infarcted heart tissue. Again, the increase was small compared with that of the competitive complement components. These data indicate that the forces which upregulate and activate complement in AD and myocardial infarction are not effectively suppressed by the endogenous regulators, C1-inh and CD59.
Yasojima
K
K
Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada.
McGeer
E G
EG
McGeer
P L
PL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology; D018957:CD59 Antigens / Q000235:genetics / Q000378:metabolism*; D003172:Complement C1 / Q000378:metabolism*; D003174:Complement C1 Inactivator Proteins / Q000235:genetics / Q000378:metabolism*; D050718:Complement C1 Inhibitor Protein; D017931:DNA Primers; D018728:Entorhinal Cortex / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis
D018957:CD59 Antigens; D003172:Complement C1; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D017931:DNA Primers; D012333:RNA, Messenger