Situating tau pathology and neuroinflammation along the principal gradients of brain organisation in Alzheimer’s disease

The spread of abnormal tau along connectivity‐based networks is a hallmark of Alzheimer’s disease (AD). In addition, activated microglia was shown to affect tau spread across networks. However, traditional network approaches using atlas‐defined regions suffer from assuming within‐region homogenous connectivity, as well as abrupt and linear connectivity changes between the regions; while, in fact, brain structure and function exist as complex overlapping axes of connectivity variation. Here, we studied smooth/continuous spatial transitions or ‘gradients’ of connectivity and their link to gradients of pathology in AD. This work provides novel insights into brain architecture driving pathology spread.