Evidence that immunoglobulin-positive neurons in Alzheimer's disease are dying via the classical antibody-dependent complement pathway

A recent study provided evidence that immunoglobulins (Igs) are not only present in Alzheimer's disease (AD) brains, but are also immunohistochemically detected in and/or on a particular population of pyramidal neurons that appeared morphologically degenerative in contrast to neighboring normal-appearing Ig-negative neurons. Because little has been reported about these Ig-positive neurons, the objectives of this study were to characterize the inflammatory profile of these neurons in the AD brain by determining if they possess complement components and are associated with reactive microglia. The data showed that the Ig-positive neurons had complement C1q and C5b-9 proteins and appeared degenerative. Furthermore, D-related human leukocyte antigen (HLA-DR)-positive fibers of reactive microglia were spatially closer (p < 0.001) and often in contact with the Ig-positive neurons than the Ig-negative neurons. Collectively, these data suggest that the Ig-positive neurons detected in AD brains are dying from the processes of the antibody-induced classical complement pathway.