It has been described that the APOE ε4 allele affects brain connectivity in known early-stage Alzheimer’s disease regions.55 Moreover, a different gene expression in various brain regions is associated with shred susceptibility to Alzheimer’s disease pathology such as tau deposition and neurodegeneration.56-58 The mechanistic pathway of vulnerability to disruption in FC in Alzheimer’s disease progression encompasses many different factors such as genetic features, copathologies, neuroinflammation and Alzheimer’s disease core pathology hallmarks, which warrant further research. The gene discussed is MAPT; the disease is early-onset autosomal dominant Alzheimer disease.