Transport of prion protein across the blood–brain barrier

The cellular form of the prion protein (PrPc) is necessary for the development of prion diseases and is a highly conserved protein that may play a role in neuroprotection. PrPc is found in both blood and cerebrospinal fluid and is likely produced by both peripheral tissues and the central nervous system (CNS). Exchange of PrPc between the brain and peripheral tissues could have important pathophysiologic and therapeutic implications, but it is unknown whether PrPc can cross the blood–brain barrier (BBB). Here, we found that radioactively labeled PrPc crossed the BBB in both the brain-to-blood and blood-to-brain directions. PrPc was enzymatically stable in blood and in brain, was cleared by liver and kidney, and was sequestered by spleen and the cervical lymph nodes. Circulating PrPc entered all regions of the CNS, but uptake by the lumbar and cervical spinal cord, hypothalamus, thalamus, and striatum was particularly high. These results show that PrPc has bidirectional, saturable transport across the BBB and selectively targets some CNS regions. Such transport may play a role in PrPc function and prion replication.