Progression of cerebral amyloid load is associated with the apolipoprotein E ε4 genotype in Alzheimer's disease.

Abstract

BACKGROUND:

Pittsburgh Compound B ([¹¹C] PiB) is a specific positron emission tomography (PET) marker of cerebral amyloid deposits. Only few data have been published on in vivo longitudinal changes of amyloid load in Alzheimer's disease (AD) patients, with conflicting results. Therefore, little is known about the factors that influence these changes.

METHODS:

A group of 24 patients with probable AD diagnosed by combining established clinical criteria with an AD-typical pattern in [(18)F] fluoro-deoxy-glucose PET underwent [¹¹C] PiB-PET examinations at baseline and after 24 months. The difference of amyloid load between the two examinations and the association with clinical and neurobiological variables was examined with a regions-of-interest approach and voxel-based analyses.

RESULTS:

Cerebral [¹¹C] PiB uptake ratio increased significantly by an annual rate of 3.92%. Although the increase occurred in all parts of the neocortex, no increase was detected in the archipallium. The increase was gene-dose-dependent (analysis of variance p = .012) to the number of apolipoprotein E ε4 alleles. Progression of dementia symptoms was correlated to the [¹¹C] PiB increase in numerous regions associated with cognition.

CONCLUSIONS:

The results of this study indicate that a significant increase of amyloid deposition occurs in patients with AD during a relatively short interval of its clinical course. The rate of amyloid aggregation rate is closely associated with the apolipoprotein E genotype, which might be important for the evaluation of antiamyloid drug treatment effects. The present study further emphasizes the value of amyloid-plaque imaging as a marker of disease progression and as a potential surrogate marker to be used in antiamyloid drug trials.

• Authors: Timo Grimmer, Susanne Tholen, Behrooz H Yousefi, Panagiotis Alexopoulos, Annette Förschler, Hans Förstl, Gjermund Henriksen, William E Klunk, Chester A Mathis, Robert Perneczky, Christian Sorg, Alexander Kurz, Alexander Drzezga
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 68 Issue 10 Pg. 879-84 (Nov 15 2010) ISSN: 1873-2402 [Electronic] United States
• PMID: 20598287 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Chemical References

• 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
• Aniline Compounds
• Apolipoprotein E4
• Radiopharmaceuticals
• Thiazoles
• Fluorodeoxyglucose F18

Topics

• Aged
• Alzheimer Disease (diagnostic imaging, genetics, metabolism)
• Aniline Compounds
• Apolipoprotein E4 (genetics)
• Brain (diagnostic imaging, metabolism)
• Disease Progression
• Female
• Fluorodeoxyglucose F18
• Genotype
• Humans
• Male
• Middle Aged
• Plaque, Amyloid (metabolism)
• Positron-Emission Tomography (methods)
• Radiopharmaceuticals
• Thiazoles