Secreted forms of β-amyloid precursor protein protect against ischemic brain injury

The β-amyloid precursor protein (βAPP) is the source of the amyloid β- peptide that accumulates in the brain in Alzheimer's disease. A major processing pathway for βAPP involves an enzymatic cleavage within the amyloid β-peptide sequence that liberates secreted forms of βAPP (APP(s)s) into the extracellular milieu. We now report that postischemic administration of these APP(s)s intracerebroventricularly protects neurons in the CA1 region of rat hippocampus against ischemic injury. Treatment with APP(s)695 or APP(s)751 resulted in increased neuronal survival, and the surviving cells were functional as demonstrated by their ability to synthesize protein. These data provide direct evidence for a neuroprotective action of APP(s)s in vivo.