title: Cerebrospinal fluid amyloid beta(40) is decreased in cerebral amyloid angiopathy.
abstract: Cerebral amyloid angiopathy is caused by deposition of the amyloid beta protein in the cerebral vasculature. In analogy to previous observations in Alzheimer disease, we hypothesized that analysis of amyloid beta(40) and beta(42) proteins in the cerebrospinal fluid might serve as a molecular biomarker. We observed strongly decreased cerebrospinal fluid amyloid beta(40) (p < 0.01 vs controls or Alzheimer disease) and amyloid beta(42) concentrations (p < 0.001 vs controls and p < 0.05 vs Alzheimer disease) in cerebral amyloid angiopathy patients. The combination of amyloid beta(42) and total tau discriminated cerebral amyloid angiopathy from controls, with an area under the receiver operator curve of 0.98. Our data are consistent with neuropathological evidence that amyloid beta(40) as well as amyloid beta(42) protein are selectively trapped in the cerebral vasculature from interstitial fluid drainage pathways that otherwise transport amyloid beta proteins toward the cerebrospinal fluid.
authors.affiliation: Department of Neurology, Radboud University Nijmegen Medical Center, Donders Center for Brain, Cognition and Behavior, Nijmegen, The Netherlands. m.verbeek@cukz.umcn.nl
authors.forename: Marcel M
authors.initials: MM
authors.lastname: Verbeek
authors.forename: Berry P H
authors.initials: BP
authors.lastname: Kremer
authors.forename: Marcel Olde
authors.initials: MO
authors.lastname: Rikkert
authors.forename: Peter H M F
authors.initials: PH
authors.lastname: Van Domburg
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Skehan
authors.forename: Steven M
authors.initials: SM
authors.lastname: Greenberg
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D019540:Area Under Curve; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016657:Cerebral Amyloid Angiopathy / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000235:genetics; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D012372:ROC Curve; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins