Beta Amyloid in Alzheimer's Disease: Increased Deposition in Brain Is Reflected in Reduced Concentration in Cerebrospinal Fluid

Timo Grimmer, Matthias Riemenschneider, Hans Förstl, Gjermund Henriksen, William E. Klunk, Chester A. Mathis, Tohru Shiga, Hans Jürgen Wester, Alexander Kurz, Alexander Drzezga

Research output: Contribution to journalArticlepeer-review

240 Scopus citations

Abstract

Background: A decreased concentration of beta amyloid (1-42) (Aβ42) has consistently been found in the cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) and is considered a diagnostic biomarker. However, it is not clear to which extent CSF Aβ42 levels are reflective of cerebral pathology in AD. The aim of the study was to determine the association between cerebral amyloid plaque load, as measured by means of the positron emission tomography (PET) tracer carbon-11-labeled Pittsburgh Compound B ([11C]PiB) and CSF Aβ42 in AD. Methods: A group of 30 patients with probable AD, as defined by established clinical criteria and by an AD-typical pattern of tracer uptake in fluorine-18-labeled fluorodeoxyglucose ([18F]FDG) PET, were included. In all patients, [11C]PiB PET and CSF analysis were performed. The association between amyloid load and CSF Aβ42 levels was examined in three different ways: by linear regression analysis using an overall [11C]PiB value for the entire cerebrum, by correlation analyses using [11C]PiB measurements in anatomically defined regions of interest, and by voxel-based regression analyses. Results: All patients showed a positive [11C]PiB scan demonstrating amyloid deposition. Linear regression analysis revealed a significant inverse correlation between the overall [11C]PiB uptake and CSF Aβ42 levels. Voxel-based regression and regional correlation analyses did not attain statistical significance after correction for multiple comparisons. Numerically, correlation coefficients were higher in brain regions adjacent to CSF spaces. Conclusions: The study demonstrates a moderate linear negative association between cerebral amyloid plaque load and CSF Aβ42 levels in AD patients in vivo and suggests possible regional differences of the association.

Original languageEnglish
Pages (from-to)927-934
Number of pages8
JournalBiological Psychiatry
Volume65
Issue number11
DOIs
StatePublished - 1 Jun 2009
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Aβ42
  • CSF
  • Pittsburgh Compound B
  • [C]PiB
  • [F]FDG
  • positron emission tomography

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