Developing biomarkers for cerebral amyloid angiopathy trials: do potential disease phenotypes hold promise? – Authors’ reply

We appreciate the insightful comments from Andreas Charidimou and Hans Rolf Jäger regarding the distinct phenotypes associated with cerebral amyloid angiopathy and their effect on selection of outcome markers for clinical trials.¹ As the authors correctly note, cerebral amyloid angiopathy is a complex entity that can follow several different pathways, each associated with its own cluster of biomarkers. It follows that a key factor in selection of outcome markers for a trial of cerebral amyloid angiopathy is the pathophysiological target of the particular treatment under investigation.

Although studies of phenotypes of cerebral amyloid angiopathy often focus on the extreme forms (such as microbleeders and macrobleeders), most patients probably fall into a mixed category in which various cerebral amyloid angiopathy-related vascular processes coexist. We therefore encourage investigators of cerebral amyloid angiopathy to collect and analyse a full range of measures of focal injury and overall brain structure and function.