Cerebral Amyloid Angiopathies

The cerebral amyloid angiopathies comprise a heterogeneous group of disorders that are characterized clinically by ischaemic and/or haemorrhagic strokes, and histologically by deposition of amyloid in the wall of leptomeningeal and cerebral cortical blood vessels. On the basis of the molecular composition of the amyloid, two forms can be distinguished. Cystatin C amyloid angiopathy is a rare autosomal dominant disorder confined to several families from Iceland. beta-amyloid cerebral amyloid angiopathies may be hereditary or sporadic, and share clinical, pathological and biochemical features with Alzheimer's disease. Both types of vascular amyloid derive from precursor proteins synthesized in situ by astrocytes (cystatin C) or smooth muscle cells (beta-amyloid), and induce progressive degeneration of smooth muscle cells, blood vessel rupture and haemodynamic changes. In recent years, it has been reported that mutations underlying both types of hereditary cerebral amyloid angiopathy directly involve the gene encoding the precursor protein. These findings have increased our understanding of the amyloidogenic mechanisms and allowed preclinical diagnosis. Nevertheless, the aetiopathogenetic factors involved in the more frequent sporadic form of amyloid angiopathy remain unknown.