Cerebral Amyloid Angiopathy (CAA)

CAA is an age-related brain disorder characterized by deposition of amyloid A-beta 40 within the wall of leptomeningeal and intra-cortical arterioles (and to a lesser degree parenchymal capillaries), eventually causing either or both arteriolar rupture and occlusion, for which there is currently no treatment. CAA has attracted considerable interest in... read morethe last two decades when it emerged as a major cause of hemorrhagic stroke after 50 years of age and a significant contributor of age-related cognitive decline. Furthermore, while previously CAA could be only diagnosed using histopathological analysis of brain tissue (biopsy or post-mortem), the Harvard group demonstrated in the late 90s that a probabilistic in-vivo diagnosis of CAA could be made using blood-sensitive MRI sequences, with clinically useful accuracy. This quantum leap in turn allowed a surge of clinical and imaging studies on patient cohorts diagnosed using MRI. More recently, additional non-hemorrhagic MR as well as CT-based hemorrhagic diagnostic markers have been identified and are the subject of extensive research. Still there is room for substantial improvement in accuracy of the clinical diagnosis of CAA, for instance using CSF- or blood-based biomarkers and amyloid PET, while in parallel the spectrum of clinical presentations of CAA is enlarging. Finally, understanding the mechanisms underlying amyloid deposition in vascular walls and the relationships between CAA and Alzheimer’s disease, as well as developing widely applicable and representative animal models, are necessary steps towards the discovery of disease-modifying agents.