Main features of hereditary cerebral amyloid angiopathies: A systematic review

The term Cerebral Amyloid Angiopathy (CAA) refers to a group of neurovascular disorders characterized by amyloid deposition within the walls of leptomeningeal and cortical blood vessels of the brain, with specific predilection for arterioles, and (less often) capillaries and veins. Most CAA cases in the general population are sporadic in nature, and represent primarily an age-related condition affecting individuals in the fifth decade of life and beyond. Sporadic CAA is caused by deposition of amyloid-β (Aβ), originating from proteolytic cleavage of the Amyloid Precursor Protein (APP), within the walls of cerebral small caliber vessels. However, hereditary forms of CAA have also been described, generally presenting as rare familial disorder with monogenic (predominantly autosomal dominant) inheritance patterns. Hereditary CAA forms tend to affect younger individuals, and their course and clinical progression is more severe. Studies to date primarily focused on the vascular manifestations of sporadic and hereditary CAA, chiefly symptomatic lobar Intracerebral Hemorrhage (ICH). However, in the past decade sporadic CAA has also been consistently linked to progressive neurocognitive, neurobehavioral, and neuropsychiatric symptoms. This systematic review focuses on the genetics, pathogenesis, neuroimaging, neuropathology, and clinical manifestations of hereditary CAA with specific emphasis on previously overlooked cognitive, behavioral, and psychiatric symptoms.