Hereditary and sporadic forms of A<tex>$\beta$</tex>-cerebrovascular amyloidosis and relevant transgenic mouse models
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
International journal of molecular sciences
, p. 1872-1895
University of Antwerp
Cerebral amyloid angiopathy (CAA) refers to the specific deposition of amyloid fibrils in the leptomeningeal and cerebral blood vessel walls, often causing secondary vascular degenerative changes. Although many kinds of peptides are known to be deposited as vascular amyloid, amyloid-â (Aâ)-CAA is the most common type associated with normal aging, sporadic CAA, Alzheimers disease (AD) and Downs syndrome. Moreover, Aâ-CAA is also associated with rare hereditary cerebrovascular amyloidosis due to mutations within the Aâ domain of the amyloid precursor protein (APP) such as Dutch and Flemish APP mutations. Genetics and clinicopathological studies on these familial diseases as well as sporadic conditions have already shown that CAA not only causes haemorrhagic and ischemic strokes, but also leads to progressive dementia. Transgenic mouse models based on familial AD mutations have also successfully reproduced many of the features found in human disease, providing us with important insights into the pathogenesis of CAA. Importantly, such studies have pointed out that specific vastopic Aâ variants or an unaltered Aâ42/Aâ40 ratio favor vascular Aâ deposition over parenchymal plaques, but higher than critical levels of Aâ40 are also observed to be anti-amyloidogenic. These data would be important in the development of therapies targeting amyloid in vessels.