Cerebral amyloid angiopathies are vascular diseases caused by the accumulation of an amyloid substance in the walls of the small blood vessels in the meninges and cerebral cortex.
The term " amyloid" is used to describe the accumulation of insoluble proteins with a pleated beta-sheet configuration and a fibrillary structure that produces specific color in the vessel walls with the use of congo red stains.). Various types of protein have these physical characteristics and can cause the formation of amyloid deposits in the blood vessels.
Amyloid deposits can sometimes result in very serious damage to the wall of the blood vessel and particularly to the smooth muscle cells of the media layer. Such structural changes can cause arterial rupture or lumen narrowing, associated vith a decrease of the blood supply to the brain. These features explain the appearance of the cerebral lessions associated with severe forms of amyloid angiopathy i.e. major and minor haemorrhages, lesions in the white matter and small-infarcts. These cerebral lesions are responsible for the majority of neurological symptoms.
Within the cerebral amyloid angiopathies (CAA), there are sporadic (or non familial) forms in the vast majority of case and characterised by the accumulation of Aß protein in the arterial wall. I
The familial forms of CAA are unusual. They are autosomal dominant and result from errors in various genes that code for a range of proteins leading to amyloid vascular deposits:
- hereditary Aß CAA (Dutch, Flemish and Iowa type):
- type of amyloid peptide = peptide Aß
- mutations of the APP gene (Aß precursor protein) on chromosome 21
- hereditary cystatin-C CAAs (Icelandic type):
- nature of the amyloid peptide = cystatin-C
- mutation of the cystatin-C gene, chromosome 20
- familial oculoleptomeningeal amyloidosis:
- nature of the amyloid peptide = transthyretin
- mutation of the transthyretin gene, chromosome 18
- gelsolin amyloidosis (Finnish type):
- type of amyloid peptide = gelsolin
- mutation of the gelsolin gene, chromosome 9
- hereditary British-type CAAs:
- nature of the amyloid peptide = Bri protein
- mutation of the BRI gene, chromosome 13