Prion protein immunoreactivity in brain samples from an unselected autopsypopulation: findings in 200 consecutive cases

Immunostaining for prion protein (PrP) using the KG9 monoclonal antibody wa s undertaken on brain sections from an unselected group of 200 post-mortem cases. One case of clinically diagnosed vCJD was confirmed and showed wides pread abundant PrP immunostaining with KG9 and somewhat less abundant PrP w ith another monoclonal antibody, 3F4. PrP immunostaining seen with KG9 was insensitive to proteinase K pretreatment in sections from this case of vCJD . Among the remaining 199 cases, sections from 84 (42%) showed small amount s of PrP immunoreactivity with the KG9 antibody, mainly localized to neuron es, neural processes and argyrophilic plaques of the type seen in ageing an d Alzheimer's disease. Purkinje cells, swollen (ischaemic) axons, macrophag es and microglials cells were also occasionally labelled with this antibody in non-CJD cases. Pre-treatment of adjacent sections from non-CJD cases wi th positive KG9 staining abolished this staining, indicating that it repres ented the cellular form of PrP. There were differences in age, sex and caus e of death in non-CJD cases with some PrP immunostaining patterns compared with cases lacking any staining. Specifically, a younger mean age, more fem ales and fewer cardiac deaths were found among those with neuronal PrP stai ning patterns. Staining of some features was also significantly associated. These findings need to be taken into account when PrP immunostaining is us ed to diagnose prion diseases. They may indicate that cellular PrP is incre ased in the human brain under some circumstances and provide insight into t he handling of this protein by human brain cells.