title: Cerebral amyloid angiopathy plays a direct role in the pathogenesis of Alzheimer's disease. Pro-CAA position statement.
abstract: For the purposes of this debate here we argue the case that cerebral amyloid angiopathy (CAA) has a direct role in the pathogenesis of Alzheimer's disease (AD). Firstly, there is a very close relationship between CAA and AD and they share genetic risk factors. Secondly, we propose a specific mechanism which puts age-related cerebrovascular degeneration at a crucial point in the pathogenesis of AD as follows. Amyloid beta-protein (Abeta) is normally eliminated from the brain along with extracellular fluid by bulk flow along the perivascular pathway. Age-related fibrosis of cerebral cortical and meningeal arteries leads to impaired drainage of Abeta along the perivascular pathway and, together with the production of Abeta by smooth muscle cells and perivascular cells, is responsible for accumulation of Abeta as CAA. Reduced elimination leads to increased concentration of soluble Abeta in the extracellular fluid of the brain parenchyma. Increased concentration of soluble Abeta leads to the formation of insoluble Abeta plaques, other features of AD pathology, and dementia.
authors.affiliation: Clinical Neurosciences, University of Southampton, Southampton General Hospital, Mailpoint 813, Southampton, SO 16 6YD, UK. j.Nicoll@soton.ac.uk
authors.forename: James A R
authors.initials: JA
authors.lastname: Nicoll
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
authors.forename: Janusz
authors.initials: J
authors.lastname: Frackowiak
authors.forename: Bozena
authors.initials: B
authors.lastname: Mazur-Kolecka
authors.forename: Roy O
authors.initials: RO
authors.lastname: Weller
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D016657:Cerebral Amyloid Angiopathy / Q000150:complications* / Q000235:genetics / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D012307:Risk Factors
chemical_list: D016229:Amyloid beta-Peptides