Cellular prion protein (PrPc) is a high affinity receptor for soluble oligomeric AB42 (see Figure 2,
Strittmater et al., 2010), mediating toxic effects on synaptic plasticity. PrPc represents a target in
Alzheimer?s disease (AD) directly disrupting the signaling pathway of soluble A?42.

Please aIDress the following questions.

1) Describe an in vivo experiment that would validate this target as a disease modifying therapy for AD using
a specific monoclonal anti-PrPc antibody. In your answer justify and describe your chosen disease animal model
of AD, treatment groups and chosen endpoints to measure disease modification. Discuss the validity of your
chosen disease animal model.

2) Define the term pharmacodynamic (PD) marker. Describe why PD markers are essential to any drug development
programme. P10.40ropose a possible PD marker for an anti-PrPc antibody.

To help you aIDress the questions above refer to the attached publications Chung et al., 2010 and Strittmater
et al., 2010, my lecture notes (TSM and TP), in vivo experimental design practical notes as well as aIDitional
reading