The neuroprotective domains of the amyloid precursor protein, in traumatic brain injury, are located in the two growth factor domains

► sAPPα has three functional domains: D1, D2 and D6a. ► Only the D1 and D6a domains contain heparin binding sites. ► Treatment with the D1 and D6a domains improves outcome after traumatic brain injury. ► The D2 domain had no effect. ► sAPPα may act through its heparin binding sites to confer its neuroprotective activity.