Serum amyloid P component accumulates and persists in neurones following traumatic brain injury

The mechanisms underlying neurodegenerative sequelae of traumatic brain injury (TBI) are poorly understood. The normal plasma protein, serum amyloid P component (SAP), which is normally rigorously excluded from the brain, is directly neurocytotoxic for cerebral neurones and also binds to A beta amyloid fibrils and neurofibrillary tangles, promoting formation and persistence of A beta fibrils. Increased brain exposure to SAP is common to many risk factors for dementia, including TBI, and dementia at death in the elderly is significantly associated with neocortical SAP content. Here, in 18 of 30 severe TBI cases, we report immunohistochemical staining for SAP in contused brain tissue with blood-brain barrier disruption. The SAP was localized to neurofilaments in a subset of neurones and their processes, particularly damaged axons and cell bodies, and was present regardless of the time after injury. No SAP was detected on astrocytes, microglia, cerebral capillaries or serotoninergic neurones and was absent from undamaged brain. C-reactive protein, the control plasma protein most closely similar to SAP, was only detected within capillary lumina. The appearance of neurocytotoxic SAP in the brain after TBI, and its persistent, selective deposition in cerebral neurones, are consistent with a potential contribution to subsequent neurodegeneration.