MAPT and Alzheimer disease: In 2010, Jack et al. proposed a hypothetical model of AD biomarkers in which Aβ biomarkers become abnormal first (i.e., decreased CSF Aβ42 level and/or Aβ PET positivity) sequentially followed by tau pathology (i.e., increased CSF p-tau and/or Tau PET positivity), neurodegenerative biomarkers and cognitive symptoms [15].