Immunohistochemical investigation of the brain of aged dogs. I. Detection of neurofibrillary tangles and of 4-hydroxynonenal protein, an oxidative damage product, in senile plaques

In the aging dog brain lesions develop spontaneously. They share some morph ological characteristics with those of Alzheimer's disease in man. Diffuse and primitive plaques are well known, whereas neuritic plaques rarely devel op. Neurofibrillary tangles have not been seen in the canine. The aim of th e present investigation was to study major age-related changes of the dog's brain using paraffin sections with respect to cross-immunoreactivity of ta u, A beta protein and other immunoreactive components including hydroxynone nal protein, which is a marker for oxidative damage. The occurrence of neur ofibrillary tangles and of the protein tau therein was studied in serial br ain sections of two dogs with the Gallyas stain and by immunohistochemistry with three different antibodies against tau. Senile plaques were stained w ith a monoclonal anti-A beta (residues 8-17), polyclonal anti-apolipoprotei n E and a monoclonal antibody against 4-hydroxynonenal (HNE). Amyloid depos its and controls were screened by Congo red staining viewed in fluorescent light, followed by polarized light for green birefringence. With the Gallyas stain and one ofthe antisera against tau, neurofibrillary tangles were revealed in a similar dispersed pattern, whereas the other ant itau antisera gave negative results. With the anti-HNE a positive reaction was found in cerebral amyloid deposits and in vascular wall areas where amy loid deposition was confirmed by Congored staining, and in perivascular cel ls and in some neurons. These results indicate that the canine with his tan gles and plaques which show oxidative changes, forms a spontaneous model fo r understanding the early; changes and their interrelationships in Alzheime r's disease.