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-re cognizing monoclonal antibodies AT8, AT100, PHF-1 and TC-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 su lphate proteoglycan-rich perineuronal nets of the extracellular matrix, suc h polyanionic lattice-like neuronal coatings were revealed lectin- and immu nocytochemically. Hyperphosphorylated tau was exclusively observed in neuro ns devoid of perineuronal nets. The present findings in the aged bison para llel previously obtained results from a quantitative study of human brains affected by Alzheimer's disease. In conclusion, the low susceptibility of d ifferent types of neurons to the abnormal phosphorylation of tau correspond s to high proportions of certain chondroitin sulphate proteoglycans in thei r microenvironment. (C) 2001 Elsevier Science Inc. All rights reserved.