Causes
CAA has been identified as occurring either sporadically (generally in elderly populations) or in familial forms such as Flemish, Iowa, and Dutch types. Sporadic forms of CAA have been further characterized into two types based on deposition of amyloid β-protein (Aβ) in cortical capillaries. In all cases, it is defined by the deposition of Aβ in the leptomeningal and cerebral vessel walls.
The reason for increased deposition of Aβ in sporadic CAA is still unclear with both increased production of the peptide and abnormal clearance having been proposed as potential causes. Under normal physiology Aβ is cleared from the brain by four pathways: (1) endocytosis by astrocytes and microglial cells, (2) enzymatic degradation by neprilysin or insulysin (3) cleared by way of the blood brain barrier or (4) drained along periarterial spaces. Abnormalities in each of these identified clearance pathways have been linked to CAA.
In familial forms of CAA, the cause of Aβ build up is likely due to increased production rather than poor clearance. Mutations in the amyloid precursor protein (APP), Presenilin (PS) 1 and PS2 genes can result in increased rates of cleavage of the APP into Aβ.
An immune mechanism has also been proposed.
Read more about this topic: Cerebral Amyloid Angiopathy