MAPT and early-onset autosomal dominant Alzheimer disease: Multifactorial mechanisms involving abnormalities in CSF and plasma biomarkers such as t-tau and p-tau and spatiotemporal alterations in brain amyloid-beta peptide deposition from the ADNI cohort suggest that vascular dysregulation is the strongest and earliest pathological event concomitant with late-onset Alzheimer’s disease [135].