In response to Kessels et al
Juha Laurén1, David A. Gimbel1, Haakon B. Nygaard1, John W. Gilbert1 & Stephen M. Strittmatter1
Amyloid-? oligomers are correlated with Alzheimer’s disease progression and suppress synaptic plasticity1, 2, 3. Through unbiased expression cloning, we identified cellular prion protein (PrPC) as an amyloid-? oligomer binding protein4. PrPC was necessary for acute amyloid-?(1?42) (A?42) oligomer suppression of synaptic plasticity4; thus, it becomes critical to explore the importance of PrPC in a range of Alzheimer’s-disease-related deficits. Transgenic Alzheimer’s disease model mice show deficits of spatial learning and memory5, so the most direct assessment of PrPC will monitor memory in transgenic Alzheimer’s disease model mice deficient for PrPC. In this paradigm, amyloid-? species are produced endogenously and the brain is exposed chronically over months. Recently, we have found that deletion of PrPC from APPswe/PSen1?E9 transgenic mice restores spatial learning and memory without altering amyloid-?6. Furthermore, the early death, synapse loss and serotonin axonal degeneration of transgenic Alzheimer’s disease mice require PrPC (ref. 6). Kessels et al.7 examine PrPC in alternative paradigms.