Vacuolar degeneration affecting brain macrophages/microglia in variant CJD: a report on two cases.

We present the neuropathology of two cases of variant Creutzfeldt-Jakob disease (vCJD) showing significant vacuolar degenerative alterations specifically affecting brain macrophages/microglia within the thalamus and, to a lesser extent, within the neocortical grey matter. Vacuolar degeneration in these cells was extensive, and likely to be associated with the development of a uniform sub-type of 'spongiform' vacuole seen in vCJD. The extensive morphological alterations described here closely resemble those very recently reported by Zucconi and colleagues, in response to experimental copper deficiency induced through dietary restriction, but could not be detected in cases of sporadic CJD examined. The significance of these novel findings are discussed in relation to copper homeostasis, loss of function of cellular prion protein and aberrant lysosomal catabolism within brain macrophages/microglia. This type of vacuolation may constitute a component of the overall profile of spongiform changes associated with vCJD.