LOCALIZATION AND CELL ASSOCIATION OF C1Q IN ALZHEIMERS-DISEASE BRAIN

The complement protein, Clq, has been shown to bind to fibrillar beta- amyloid, resulting in the activation of the classical complement pathw ay. Clq has also been found associated with most but not all amyloid d eposits in brain. To determine whether Clq is exclusively associated w ith plaques containing the fibrillar form of beta-amyloid, normal and Alzheimer brain were immunohistochemically double labeled using thiofl avine, which specifically stains beta-amyloid in a beta-sheet conforma tion, and an affinity-purified antibody to human Clq. Clq immunostaini ng was colocalized with nearly all thioflavine-positive plaques, while Clq was not detected in beta-amyloid immunopositive plaques which wer e thioflavine-negative. beta-amyloid plaques in nondemented controls ( which are typically thioflavine-negative) were also negative for Clq. Microglia and astrocytes of reactive morphology were also associated w ith Clq-positive plaques and neurons. Interestingly, many neuronal cel ls in the AD brain, but not microglia or astrocytes, stained prominent ly with anti-C1q. Neurons in control brain were not Clq positive. Our data suggest that some of these Clq-positive structures were neurofibr illary tangles immunoreactive for hyperphosphorylated tau, which may b e binding extracellular Clq. However, a large number of the C1q-positi ve neurons had intact cell morphology, suggesting that these cells may be synthesizing this critical complement component, Since the presenc e of Clq suggests the activation of complement and/or the activation o f proinflammatory events, and the specific class of plaques that conta in Clq are the type that corresponds to observed clinical dementia, th ese findings further support the hypothesis that complement plays a ro le in the pathogenesis of AD. (C) 1996 Academic Press, Inc.