APOE and Alzheimer disease: For example, in the specific context of AD - where entorhinal cortex lesions represent some of the very initial pathogenetic events ending in the synaptic loss subjacent memory impairment - it has been demonstrated that APOE4 is associated to a reduced capacity to form new synapses as measured by GAP-43 and synaptophysin proteins, which are typical molecular markers of neo-synaptogenesis [288,289].