Complement association with neurons and beta-amyloid deposition in the brains of aged individuals with down syndrome

To study the link between beta -amyloid (A beta) and neuroinflammation, we examined the levels of complement as a function of age and extent of AP dep osition in Down Syndrome (DS) brain. C1q, the first component of the comple ment cascade, was visualized using immunohistochemistry in the frontal, ent orhinal cortex, and hippocampus of 12 DS ranging from 31 to 69 years of age . C1q was consistently associated with thioflavine-S positive A beta plaque s in DS brain and increased with more extensive age-dependent. A beta depos ition. In contrast, little or no C1q labeling was associated with diffuse o r thiofiavine-S negative A beta deposits. Neurons in the hippocampus and en torhinal cortex, but less frequently in frontal cortex, were C1q positive i n DS cases with sufficient neuropathology to have a diagnosis of Alzheimer' s disease. C1q-positive neurons were associated with activated microglia. T hese results provide evidence for A beta -mediated inflammatory factors con tributing to the rapid accumulation of neuropathology in DS brain. (C) 2001 Academic Press.