Hereditary and sporadic forms of abeta-cerebrovascular amyloidosis and relevant transgenic mouse models.
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-beta (Abeta)-CAA is the most common type associated with normal aging, sporadic CAA, Alzheimer's disease (AD) and Down's syndrome. Moreover, Abeta-CAA is also associated with rare hereditary cerebrovascular amyloidosis due to mutations within the Abeta 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 Abeta variants or an unaltered Abeta42/Abeta40 ratio favor vascular Abeta deposition over parenchymal plaques, but higher than critical levels of Abeta40 are also observed to be anti-amyloidogenic. These data would be important in the development of therapies targeting amyloid in vessels.
Kumar-Singh
Samir
S
Neurodegenerative Brain Diseases Group, VIB Department of Molecular Genetics, University of Antwerp, Antwerpen - CDE, Universiteitsplein 1, B-2610, Antwerpen, Belgium.|Laboratory of Neurogenetics, Institute Born Bunge, University of Antwerp, Antwerpen, Belgium.|University of Antwerp, Antwerpen, Belgium.
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D012307:Risk Factors
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor