Familial Cerebral Amyloid Angiopathies - Theoretical and practical information currently available

Cerebral amyloid angiopathies are vascular leukoencephalopathies caused by the presence of amyloid deposits in the walls of the blood vessels in the white matter of the brain. Most cases are sporadic but there are a number of rare, hereditary forms with autosomal dominant transmission.

In some very rare forms of familial cerebral amyloid angiopathy, mutations have been described in several genes.

  • In the Dutch type (HCHWA-D, Hereditary Cerebral Haemorrhage with Amyloidosis – Dutch type), several mutations have been reported in the amyloid peptide precursor (APP),
  • in Hereditary Cystatin-C Amyloid Angiopathy ” (HCCAA), the disease is caused by the Leu68Gln mutation in exon 2 of Cystatin-C (CST3),
  • in Familial British Dementia, the mutations occur in the BRI gene,
  • in the Finnish form (FAF, Familial amyloidosis of the Finnish type), 2 mutations have been reported in Gelsolin (GSN).

Moreover, certain mutations in transthyretin (mainly involved in peripheral types of amyloid angiopathy) cause types that are limited to the brain.

To meet the demand of clinicians, our laboratory has introduced routine partial sequencing of the genes responsible for cerebral amyloid angiopathies in the BRI genes (exons 16 and 17 of the BRI gene which code for the ABRI peptide), gelsolin (exons 4 and 5 which code for AGel peptide) and Cystatine-C (exon 2). The laboratory also carries out comprehensive sequencing of Transthyretin (4 exons).