Levels of neurogranin are elevated in the cerebrospinal fluid of people with mild cognitive impairment who carry the apolipoprotein E (APOE) ɛ4 allele, new research has shown. APOE* ɛ4 is the most important genetic risk factor for AD, but the pathophysiological link between the risk allele and AD has remained elusive. Neurogranin is a marker of synaptic injury, and the new data suggest that APOE* ɛ4 carriers are susceptible to synaptic damage manifests as cognitive decline.