MAPT and Alzheimer disease: Moreover, in preclinical AD, changes in vascular biomarkers occur before a detectable increase in standard AD biomarkers, including amyloid deposition, decreased cerebrospinal fluid (CSF) levels of Aβ42 (the most amyloidogenic form of Aβ), and increased CSF levels of tau and phosphorylated tau [47]. In close agreement, BBB integrity is compromised in transgenic AD mice from an early stage, even prior to amyloid deposition [39, 48, 49].