Transport of prion protein across the blood–brain barrier

The cellular form of the prion protein (PrP c) is necessary for the development of prion diseases and is a highly conserved protein that may play a role in neuroprotection. PrP c is found in both blood and cerebrospinal fluid and is likely produced by both peripheral tissues and the central nervous system (CNS). Exchange of PrP c between the brain and peripheral tissues could have important pathophysiologic and therapeutic implications, but it is unknown whether PrP c can cross the blood–brain barrier (BBB). Here, we found that radioactively labeled PrP c crossed the BBB in both the brain-to-blood and blood-to-brain directions. PrP c 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 PrP c 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 PrP c has bidirectional, saturable transport across the BBB and selectively targets some CNS regions. Such transport may play a role in PrP c function and prion replication.