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.

Fig 1

Scatter plots of amyloid β-peptide (Aβ)₄₂, Aβ₄₀, total tau, phosphorylated tau₁₈₁, and Aβ₄₀/Aβ₄₂ in the control, cerebral amyloid angiopathy (CAA) and Alzheimer disease (AD) groups. The CAA patient with the Iowa mutation is indicated by a short arrow, the CAA patient with the Dutch mutation by a long arrow. Mean concentration is indicated by a horizontal line. *p < 0.05; **p < 0.01; ***p < 0.001 (t tests).

Fig 2

Combination of amyloid β-peptide (Aβ)₄₀ and total tau (t-tau) analysis (A) or Aβ₄₂ and t-tau analysis (B) in the cerebral amyloid angiopathy (open circles) and control groups (closed squares).