Careful analysis of neurofibrillary changes in the brain at autopsy trace the onset of AD back to over 40 years before the onset of dementia [47, 58], and with the development of imaging of amyloid-β in the brain and cerebrospinal fluid measures of amyloid-β, there are AD-related changes measurable in living individuals at least 20 years before dementia, which are also highly related to APOE genotype [59]. Here, APOE is linked to Alzheimer disease.