We hypothesized that hippocampal volume (HV), a biomarker of neurodegeneration, may mediate the connection between the <i>NECTIN2</i> polymorphism and AD.<h4>Methods</h4>The analysis was conducted using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). This evidence concerns the gene NECTIN2 and early-onset autosomal dominant Alzheimer disease.