The exact alteration times of the different biomarkers in sporadic Alzheimer’s are not known, but in the autosomal dominant familial form with the E280A mutation in PS1 it has been discovered that carriers of the Paisa mutation show high levels of biomarkers such as ß42 in cerebrospinal fluid, NFL and phTAU in plasma at 24, 20 years before the first symptoms of Mild Cognitive Impairment. This evidence concerns the gene NEFL and Cognitive impairment.