The prion protein in human neurodegenerative disorders

We evaluate cellular prion protein (PrPc) immunoreactivity (IR) in Alzheimer's, Parkinson's, diffuse Lewy body, and motor neuron diseases (MND), progressive supranuclear palsy, and multiple system atrophy. We use immunohistochemistry for PrP, including five monoclonal antibodies against different epitopes and three different pretreatments, alpha-synuclein, phosphorylated tau, beta-amyloid, and ubiquitin. Disease-specific inclusions are devoid of PrPc IR. Using double immunofluorescence and confocal laser microscopy we observe focal overlapping of PrPc with tau and with alpha-synuclein in early, but not in fully developed inclusions. However, PrPc IR neurons may contain abnormal tau or alpha-synuclein aggregates. Additionally, we observe a loss of PrPc IR in anterior horn neurons in MIND. Our results suggest that expression of PrPc reflects a general response to cellular stress rather than specific co-operation in aggregation of other proteins. (C) 2002 Published by Elsevier Science Ireland Ltd.