Neuroaxonal pathology in Creutzfeldt-Jakob disease

Neuroaxonal pathology has met little attention in transmissible spongiform encephalopathies. In brains of a series of 39 consecutive Creutzfeldt-Jakob disease (CJD) cases, we detected numerous abnormal neurites that labeled for neurofilament proteins (NFP) by immunocytochemistry. Three types of abnormally NFP-accumulating structures were more prominently observed in CJD brains than in age-matched control brains: 1. Neurons with NFP in their somata were seen in 29 CJD cases (74%), some appearing distended with eccentrically placed nuclei and homogenously stained cytoplasm. 2. Neuritic distensions (neuritic swellings, dystrophic neurites) were observed mainly in the white matter but also at the junction between gray and white matter. In some axons many such swellings could be traced along the visible part of the axonal segment. 3. Axonal spheroids were observed mainly in the medulla, predominantly but not exlusively in posterior nuclei, and were more numerous than in age-matched control brains. Several neurons, axons and spheroids demonstrated immunoreactivity for amyloid precursor protein. Their number was much smaller, however, than that of NFP-immunoreactive structures and varied from one or two immunopositive neurites per section to small clusters of beaded or spiral axons. Focal expression of apolipoprotein E in cells of microglial and astrocytic morphology was observed in areas with most pronounced axonal damage. We conclude that neuroaxonal pathology is a frequent and important part of brain lesioning in CJD, probably reflecting profound impairment of axonal transport.