title: Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies.
abstract: In cerebral amyloid angiopathy (CAA), amyloid fibrils deposit in walls of arteries, arterioles and less frequently in veins and capillaries of the central nervous system, often resulting in secondary degenerative vascular changes. Although the amyloid-beta peptide is by far the commonest amyloid subunit implicated in sporadic and rarely in hereditary forms of CAA, a number of other proteins may also be involved in rare familial diseases in which CAA is also a characteristic morphological feature. These latter proteins include the ABri and ADan subunits in familial British dementia and familial Danish dementia, respectively, which are also known under the umbrella term BRI2 gene-related dementias, variant cystatin C in hereditary cerebral haemorrhage with amyloidosis of Icelandic-type, variant transthyretins in meningo-vascular amyloidosis, disease-associated prion protein (PrP(Sc)) in hereditary prion disease with premature stop codon mutations and mutated gelsolin (AGel) in familial amyloidosis of Finnish type. In this review, the characteristic morphological features of the different CAAs is described and the implication of the biochemical, genetic and transgenic animal data for the pathogenesis of CAA is discussed.
authors.affiliation: Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, Queen Square, London WC1N3BG, UK. t.revesz@ion.ucl.ac.uk
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
authors.forename: Janice L
authors.initials: JL
authors.lastname: Holton
authors.forename: Tammaryn
authors.initials: T
authors.lastname: Lashley
authors.forename: Gordon
authors.initials: G
authors.lastname: Plant
authors.forename: Blas
authors.initials: B
authors.lastname: Frangione
authors.forename: Agueda
authors.initials: A
authors.lastname: Rostagno
authors.forename: Jorge
authors.initials: J
authors.lastname: Ghiso
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000686:Amyloidosis / Q000150:complications / Q000235:genetics; D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D002543:Cerebral Hemorrhage / Q000150:complications / Q000235:genetics; D055316:Cystatin C / Q000235:genetics; D003704:Dementia / Q000150:complications / Q000235:genetics; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D007167:Immunotherapy; D009154:Mutation; D011228:Prealbumin / Q000378:metabolism; D017096:Prion Diseases / Q000150:complications
chemical_list: D016229:Amyloid beta-Peptides; D055316:Cystatin C; D011228:Prealbumin