Cerebral amyloid angiopathy and gene polymorphisms

J Neurol Sci. 2004 Nov 15;226(1-2):41-4. doi: 10.1016/j.jns.2004.09.009.


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 beta protein (Abeta), 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 Abeta 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 alpha1-antichymotrypsin (ACT). As for the APOE, which has been well studied for CAA as well as AD and Abeta deposition, the epsilon4 allele is found to be associated with CAA, and the epsilon2 with CAA-related hemorrhage. Recently, we investigated whether gene polymorphisms of neprilysin (NEP), an Abeta-degrading enzyme, and the transforming growth factor (TGF)-beta1 (TGF-beta1), a multifunctional cytokine implicated in Abeta 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-beta1 was also associated with the severity of CAA. These data suggest that multiple gene polymorphisms, including molecules related to the Abeta cascade, could be associated with the risk of sporadic CAA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aged
  • Animals
  • Apolipoproteins E / genetics
  • Cerebral Amyloid Angiopathy / genetics*
  • Cerebral Amyloid Angiopathy / pathology*
  • Humans
  • Neprilysin / genetics
  • Polymorphism, Genetic / genetics*


  • Apolipoproteins E
  • Neprilysin