Subcellular localization of IgG from the sera of ALS patients in the nervous system.

Immunoglobulin G (IgG) samples isolated from the sera of amyotrophic lateral sclerosis (ALS) and control patients were injected intraperitoneally into mice. After 24 h the mice were processed for immune electron microscopic immunohistochemistry to localize IgG in their nervous system. The injected ALS IgG was observed in the axon terminals of the lower motor neurons (MNs), localized to the microtubules and enriched in the rough endoplasmic reticulum (RER). In post-mortem spinal cord samples from ALS patients, IgG was similarly detected in the vicinity of the microtubules and in the RER of the MNs. IgG was neither found in the corresponding structures of MNs of mice injected with the control human IgG nor in post-mortem human control spinal cord samples. The data suggest that multiple antibodies directing to different structures of the MNs may play a role in their degeneration in ALS.