The role of co-pathologies in the clinical presentation of prion disease

Summary We will investigate the role of co-pathologies in prion disease by assessing the behavior (gait and memory), pathology (histology and western immunoblot analysis) and propagation of prions using our unique panel of mouse adapted human prion strains.

Project Details

Prion diseases are invariably fatal neurodegenerative disorders that affect both humans and animals. Prion diseases are caused by the propagation of a misfolded form of the normal cellular prion protein. A unique feature of prion diseases is their range of clinical presentations which affect memory and movement. While these features can be attributed to differences in the shape of the misfolded prion protein, we do not understand how or why prions with different shapes (prion strains) have different clinical presentations. Another recent observation is the presence of co-pathologies, or misfolded proteins associated with other neurodegenerative disorders that have either the clinical presentation of deteriorating movement (alpha-synuclein in Parkinson’s disease and TDP-43 in Motor Neuron Disease) or deteriorating memory (amyloid-beta and tau in Alzheimer’s disease). We propose that some of the clinical variation in prion disease is due to these co-pathologies and that the presence of co-pathologies is dependent on the shape (or strain) of the misfolded prion protein. We will investigate the role of co-pathologies in prion disease by assessing the behavior (gait and memory), pathology (histology and western immunoblot analysis) and propagation of prions using our unique panel of mouse adapted human prion strains.