Emerging evidence suggests that these plasma biomarkers (GFAP,NfL, pTau181, Aβ42/40) reflect processes of brain aging, even in cognitively healthyindividuals, by capturing subtle neurobiological changes linked to neuroinflammation, axonalintegrity, cerebrovascular function, and early Alzheimer-disease related pathobiology. This evidence concerns the gene NEFL and early-onset autosomal dominant Alzheimer disease.