RABBIT IGG CROSS-REACTS WITH ALZHEIMER NEUROFIBRILLARY TANGLES

Biochemical studies have demonstrated that the paired helical filament s (PHF) of Alzheimer neurofibrillary tangles are mostly made up of tau and to a lesser degree of ubiquitin and other proteins. In addition, immunocytochemical labeling of tangles with antibodies to various othe r neuronal proteins has been shown previously. We report here the labe ling of the locations of PHF, i.e., Alzheimer neurofibrillary tangles, neuropil threads and plaque neurites in tissue sections with a goat a ntiserum to rabbit IgG (GAR-T). The labeling is comparable in strength and distribution to that of tau and ubiquitin antibodies. The PHF-sta ining antibodies could be removed by absorption with native rabbit IgG but not with human IgG, IgG-depleted rabbit serum, rabbit IgG heavy c hains or light chains eluted from nitrocellulose membranes. Furthermor e, the PHF reactivity was obliterated by absorption with brain homogen ate and a fraction enriched in soluble abnormally phosphorylated tau, but not with purified bovine tau or SDS-washed preparations of the rel atively insoluble population of PHE On immunoblots of both normal huma n tau and Alzheimer abnormally phosphorylated tau-enriched preparation s, GAR-T labeled a set of three to five polypeptides in the tau region . Some of these polypeptides co-migrated with the tau bands. These res ults indicate (i) that PHF in Alzheimer's disease brain cross-react wi th a structural epitope/s present on native rabbit IgG, and (ii) that the cross-reactivity with PHF is probably due to tau.