Complement regulators Cl inhibitor and CD59 do not significantly inhibit complement activation in Alzheimer disease

Proteins characteristic of activated complement are associated with Alzheim er disease (AD) lesions. The classical complement pathway can be activated only when the influence of such endogenous regulators as C1-inhibitor (C1-i nh) and CD59 are overcome. We used the techniques of reverse transcriptase- polymerase chain reaction and Western blotting to assess the mRNA and prote in levels of C1-inh and CD59 in AD and control brains in comparison with le vels of the complement components with which they interact. The inhibitors were only slightly upregulated and then only in heavily affected areas of A D brain such as the entorhinal cortex, hippocampus, midtemporal gyrus and m idfrontal 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. Peripher al organ expression of C1-inh and CD59 mRNAs was no different in AD than co ntrols but was slightly upregulated in infarcted heart tissue. Again, the i ncrease was small compared with that of the competitive complement componen ts. These data indicate that the forces which upregulate and activate compl ement in AD and myocardial infarction are not effectively suppressed by the endogenous regulators, C1-inh and CD59. (C) 1999 Elsevier Science B.V. All rights reserved.