Cerebrospinal fluid amyloid β40 is decreased in cerebral amyloid angiopathy

Abstract

Cerebral amyloid angiopathy is caused by deposition of the amyloid β protein in the cerebral vasculature. In analogy to previous observations in Alzheimer disease, we hypothesized that analysis of amyloid β 40 and β 42 proteins in the cerebrospinal fluid might serve as a molecular biomarker. We observed strongly decreased cerebrospinal fluid amyloid β 40 (p < 0.01 vs controls or Alzheimer disease) and amyloid β 42 concentrations (p < 0.001 vs controls and p < 0.05 vs Alzheimer disease) in cerebral amyloid angiopathy patients. The combination of amyloid β 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 β 40 as well as amyloid β 42 protein are selectively trapped in the cerebral vasculature from interstitial fluid drainage pathways that otherwise transport amyloid β proteins toward the cerebrospinal fluid. Ann Neurol 2009;66:245–249