Hyperphosphorylated protein tau is restricted to neurons devoid of perineuronal nets in the cortex of aged bison

Hyperphosphorylated tau in the cortex and hippocampal formation of two aged bisons was characterized by its immunoreactivity to the phospho-epitope-recognizing monoclonal antibodies AT8, AT100, PHF-1 and TG-3. Gallyas silver staining revealed sparsely scattered cortical tangles and neuropil threads. In dual-peroxidase staining experiments, the immunocytochemical detection of vulnerable neurons was combined with the demonstration of chondroitin sulphate proteoglycan-rich perineuronal nets of the extracellular matrix. Such polyanionic lattice-like neuronal coatings were revealed lectin- and immunocytochemically. Hyperphosphorylated tau was exclusively observed in neurons devoid of perineuronal nets. The present findings in the aged bison parallel previously obtained results from a quantitative study of human brains affected by Alzheimer's disease. In conclusion, the low susceptibility of different types of neurons to the abnormal phosphorylation of tau corresponds to high proportions of certain chondroitin sulphate proteoglycans in their microenvironment.