In pre-diagnostic AD patients, both NfL and GFAP levels were significantly associated with incident disease; by comparing the two biomarkers, GFAP tended to increase even before NfL, with a larger percentage of patients showing elevated GFAP than NfL values; this data may reflect the distinct biological roles of the two biomarkers, suggesting that astrocytic activation astrogliosis might contribute to neuronal axonal damage in pre-diagnostic AD. The gene discussed is NEFL; the disease is Alzheimer disease.