Persistent activation of microglia and astrocytes further promotes neuroinflammation, worsening Aβ and tau pathology.<h4>Current limitations</h4>Single-target therapies directed at Aβ or tau have shown limited clinical success and failed to alter disease progression, underscoring the complexity of AD.<h4>Objectives</h4>In response, multi-target-directed ligands (MTDLs) have emerged as a promising strategy. Here, MAPT is linked to Alzheimer disease.