Long-term follow-up of cognitively intact subjects who developed AD versus controls revealed changes in CSF biomarker levels—namely Aβ42, Aβ42:40, total tau, p-tau-181, NFL, and brain volume and cognitive performance that preceded AD onset by up to 20 years for Aβ42, while cognitive decline emerged six years prior to AD onset [30]. This evidence concerns the gene MAPT and Alzheimer disease.