title: Amyloid β in hereditary cerebral hemorrhage with amyloidosis-Dutch type.
abstract: Hereditary cerebral hemorrhage with amyloidosis - Dutch type is an autosomal dominant hereditary disease caused by a point mutation in the amyloid precursor protein gene on chromosome 21. The mutation causes an amino acid substitution at codon 693 (E22Q), the 'Dutch mutation'. Amyloid β, the product after cleavage of the amyloid precursor protein, is secreted into the extracellular space. The Dutch mutation leads to altered amyloid β cleavage and secretion, enhanced aggregation properties, higher proteolysis resistance, lowered brain efflux transporter affinity, and enhanced cell surfaces binding. All these result in amyloid β accumulation in cerebral vessel walls, causing cell death and vessel wall integrity loss, making cerebral vessel walls in hereditary cerebral hemorrhage with amyloidosis-Dutch type more prone to rupture and obstruction, leading to hemorrhages and infarcts. Studying the effects of altered amyloid β metabolism due to mutations like the 'Dutch' provides us with a better understanding of amyloid β toxicity, also in other amyloid β diseases like sporadic cerebral amyloid angiopathy and Alzheimer's disease.
authors.forename: Juliette A
authors.initials: JA
authors.lastname: Kamp
authors.forename: Laure Grand
authors.initials: LG
authors.lastname: Moursel
authors.forename: Joost
authors.initials: J
authors.lastname: Haan
authors.forename: Gisela M
authors.initials: GM
authors.lastname: Terwindt
authors.forename: Saskia A M J
authors.initials: SA
authors.lastname: Lesnik Oberstein
authors.forename: Sjoerd G
authors.initials: SG
authors.lastname: van Duinen
authors.forename: Willeke M C
authors.initials: WM
authors.lastname: van Roon-Mom
mesh_terms: D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D028243:Cerebral Amyloid Angiopathy, Familial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009154:Mutation; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D059748:Proteolysis
chemical_list: D016229:Amyloid beta-Peptides