MAPT and Alzheimer disease: In AD, the majority of late-stage trials targeting amyloid-β (Aβ) have not translated into meaningful clinical benefit, with over 200 anti-amyloid trials failing and only limited [7], controversial approvals such as aducanumab, which was later withdrawn from the market for non-efficacy reasons [8]; tau-targeted and anti-inflammatory agents have similarly not shown clear disease modification [9].