Certainly, the vascular risk quantified by the office-based Framingham Heart Study cardiovascular disease risk score according to risk factors including anti-hypertensive treatment, systolic blood pressure, body mass index, history of diabetes, and current cigarette smoking status, and so on, has been shown to correlate with increased cortical tau accumulation in healthy older individuals.27 Thus, BBB dysregulation could exacerbate tau accumulation, which might further compromise BBB function, triggering a vicious cycle between tauopathy and BBB leakage in AD. Here, MAPT is linked to Alzheimer disease.