In APOE4 carriers with normal cognition or mild cognitive impairment (MCI), a prelude to AD, dynamic contrast-enhanced magnetic resonance imaging evidenced BBB leakage prior to tissue loss, indicating that BBB disruption is independent of Aβ and tau deposition (Ishii and Iadecola, 2020; Montagne et al., 2020). Here, MAPT is linked to Alzheimer disease.