MAPT and Alzheimer disease: Whether perfusion disruption is a cause or consequence of AD remains unclear.73,74 In a pioneering study, Iturria-Medina et al., reconstructed AD-abnormality trajectories and suggested an early role of vascular dysregulation in the AD development, which was followed by changes in Aβ deposition, metabolic dysfunction, functional impairment and structural atrophy.75 In contrast, we found that anomalous concentrations of Aβ and tau along with cortical volume loss preceded GM-CBF deficiency in AD.