Cerebral amyloid angiopathy and gene polymorphisms

Abstract 

Cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular amyloid deposition, associated with intracerebral hemorrhage and other cerebrovascular disorders and dementia. Several types of CAA have been identified in association with various amyloid proteins including amyloid β protein (Aβ), cystatin C, prion protein, ABri/ADan, transthyretin, and gelsolin. Hereditary forms of CAA are associated with mutations in the genes coding these proteins or their precursors. Sporadic CAA of Aβ type is most common in elderly individuals as well as patients with Alzheimer disease (AD). Several gene polymorphisms have been reported to be associated with sporadic CAA or CAA-related hemorrhage, including apolipoprotein E (APOE), presenilin 1 (PS1), and α1-antichymotrypsin (ACT). As for the APOE, which has been well studied for CAA as well as AD and Aβ deposition, the ɛ4 allele is found to be associated with CAA, and the ɛ2 with CAA-related hemorrhage. Recently, we investigated whether gene polymorphisms of neprilysin (NEP), an Aβ-degrading enzyme, and the transforming growth factor (TGF)-β1 (TGF-β1), a multifunctional cytokine implicated in Aβ deposition, are associated with sporadic CAA. Concerning a GT repeat polymorphism in the enhancer/promoter region of the NEP, the shorter repeat alleles were associated with the CAA severity. The T/C polymorphism at codon 10 in exon 1 of the TGF-β1 was also associated with the severity of CAA.

These data suggest that multiple gene polymorphisms, including molecules related to the Aβ cascade, could be associated with the risk of sporadic CAA.

Keywords: Cerebral amyloid angiopathy, Gene polymorphism, Amyloid β protein, Intracerebral hemorrhage, Apolipoprotein E, Neprilysin