Glia and the pathology of variant Creutzfeldt-Jakob disease (vCJD)

Glia may be implicated in the pathology of variant Creutzfeldt-Jakob disease (vCJD) in several ways: (1) glial cells could be involved in the formation of prion protein (PrP^sc) deposits, (2) PrP^sc deposits could stimulate the production of astrocytes and microglia, (3) PrPsc deposits could damage adjacent glial cells, and (4) glial cells could remove aggregates of PrPsc from the brain. To clarify the significance of glial cells in vCJD, the relationship between PrPsc deposits and their associated glia, together with neurons and blood vessels, was studied in six cases of vCJD. Multicentric PrPsc deposits were the largest and least frequent type of deposit observed and were more commonly associated with glial cells, neuronal perikarya, and blood vessels than the more common diffuse and florid PrP^sc deposits. Diffuse PrP^sc deposits were more frequently associated with glial cells and neurons than the florid deposits. The ratio of astrocytes to oligodendrocytes adjacent to PrP^sc deposits was similar to normal brain but the ratio of astrocytes or oligodendrocytes to microglia was less than in normal brain. The intensity of immunolabelling of multicentric PrPsc deposits was positively correlated with the presence of associated vacuoles and negatively correlated with the frequency of microglia. The patterns of correlation between deposit morphology and associated glial cells and neurons were similar for the diffuse and florid type PrPsc deposits. Deposit size was most consistently correlated with the number of associated neurons and vacuoles. The data suggest in vCJD: (1) there was no evidence that glia were necessary for the formation of PrPsc deposits, (2) there is an increase in microglia which may be an attempt to remove PrPsc from the bain, and (3) PrPsc deposits could affect adjacent astrocytes and damage the blood brain barrier (BBB).