Beta amyloid in Alzheimer's disease: increased deposition in brain is reflected in reduced concentration in cerebrospinal fluid.

Abstract

BACKGROUND:

A decreased concentration of beta amyloid (1-42) (Abeta42) 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 Abeta42 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 Abeta42 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 Abeta42 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 Abeta42 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 Abeta42 levels in AD patients in vivo and suggests possible regional differences of the association.

• Authors: Timo Grimmer, Matthias Riemenschneider, Hans Förstl, Gjermund Henriksen, William E Klunk, Chester A Mathis, Tohru Shiga, Hans-Jürgen Wester, Alexander Kurz, Alexander Drzezga
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 65 Issue 11 Pg. 927-34 (Jun 01 2009) ISSN: 1873-2402 [Electronic] United States
• PMID: 19268916 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
• Amyloid beta-Peptides
• Aniline Compounds
• Apolipoproteins E
• Benzothiazoles
• Carbon Radioisotopes
• Peptide Fragments
• Thiazoles
• amyloid beta-protein (1-42)
• Fluorodeoxyglucose F18

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (cerebrospinal fluid, diagnostic imaging, genetics, pathology)
• Amyloid beta-Peptides (metabolism)
• Aniline Compounds
• Apolipoproteins E (genetics)
• Benzothiazoles
• Brain (diagnostic imaging, metabolism)
• Brain Mapping
• Carbon Radioisotopes
• Female
• Fluorodeoxyglucose F18
• Humans
• Linear Models
• Magnetic Resonance Imaging (methods)
• Male
• Middle Aged
• Peptide Fragments (metabolism)
• Positron-Emission Tomography (methods)
• Thiazoles