Modifications of oligodendroglial cells in spongiform encephalopathies

Although gray matter lesions involving neurones and astrocytes are prominen t in human transmissible spongiform encephalopathies (TSE), white matter le sions have also been occasionally observed. Secondary (Wallerian) degenerat ion and direct myelin damage have been invoked, but the physiopathology of white matter involvement is still debated. We performed an immunohistochemi stry study with anti-PrP antibodies of autopsy material of four patients wi th Creutzfeldt-Jakob disease (CJD), together with transmission electron mic roscopy (TEM) studies of conventionally processed biopsy specimens of the s ame patients. Light microscopy immunolabeling was observed as arrays adjace nt to myelinic fibers and as a clumps adjacent to oligodendroglial nuclei; both cerebrum and cerebellum were involved. At the ultrastructural level, t wo types of intracellular inclusions were seen in the white matter. They we re associated with dense lysosomes in oligodendroglial perikarya and in the ir processes. The inclusions were made of finely fibrillar, paracrystalline , amorphous, or densely osmophilic material. Thus, our findings may suggest that white matter involvement in spongiform encephalopathy is due to direc t modifications of oligodendroglial cells associated with abnormal metaboli sm of PrP. (C) 1998 Academic Press.