Genetic factors for cerebral amyloid angiopathy

: Cerebral amyloid angiopathy (CAA) is cerebrovascular amyloid deposition and is related to stroke and dementia. CAA is classified into 6 types according to the biochemical properties of amyloid proteins, and among 6 types, the sporadic CAA of amyloid beta protein (Abeta) type is most frequently found in elderly people or patients with Alzheimer's disease (AD). In sporadic CAA of the Abeta type, the epsilon4 allele of the apolipoprotein E gene is associated with increased vascular Abeta deposition, while the epsilon2 allele is associated with CAA-related intracerebral hemorrhage. We have also reported that the genetic polymorphisms of presenilin-1, neprilysin, transforming growth factor beta-1, and alpha1-antichymotrypsin are associated with CAA. In the case of hereditary CAA of the Abeta type, mutations in the genes of amyloid precursor protein (APP) and presenilins have been reported. Interestingly, the missense mutations associated with CAA are located in the middle portion of Abeta, while those associated with familial AD (FAD) are near the N- or C- terminals of Abeta. Individuals with FAD with APP duplication have been reported to present with severe CAA. Some of the FAD patients with mutations in the presenilin genes and patients with Down syndrome also show CAA as a complication. Besides sporadic or hereditary CAA of the Abeta type, hereditary CAA with cerebrovascular deposition of cystatin C, transthyretin, gelsolin, prion protein, and ABri/ADan have also been reported in association with mutations in the genes of the precursor proteins. Better understanding of the genetic factors influencing CAA will lead to identification of novel diagnostic markers and the development of preventive for CAA and CAA-related disorders.