The reasons why a specific network first succumbs to pathology are unclear, although developmental factors have been suggested as predisposal factors across Alzheimer’s disease variants.122-124 In the context of the canonical, amnestic variant of Alzheimer’s disease, the APOE4 allele is known to render the temporal lobe vulnerable to pathology and neurodegeneration.241 The presence of this allele might interact with age-related processes and confers a higher vulnerability of memory systems to Alzheimer’s disease pathology. This evidence concerns the gene APOE and Alzheimer disease.