APOE and Alzheimer disease: For people with APOE genotype ε4, increasing evidence suggests that they have some defects in synaptic protection, including poor brain perfusion, slower recovery to anaerobic metabolism, more accumulation of amyloid, a cytoskeleton more vulnerable to damage, diminished growth and branching of neurites resulting in poor repair and worse N-methyl-D-aspartate (NMDA) excitotoxicity, all of which will render APOE ε4 carriers higher vulnerability to AD.