Additionally, it has been observed that ApoE4 fragmentation occurs in a brain region-dependent way, preferentially in the neocortex and hippocampus of neuron-specific enolase (NSE)-ApoE4 transgenic mice (mice expressing ApoE4 under the control of NSE promoter), being both areas very susceptible to AD-related neurodegeneration [30], as previously described in this review. This evidence concerns the gene ENO2 and Alzheimer disease.