Document Detail


Effect of APOE genotype on amyloid plaque load and gray matter volume in Alzheimer disease.
MedLine Citation:
PMID:  19339712     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To examine the influence of the APOE genotype on levels of beta-amyloid (Abeta) plaque load and atrophy in patients with Alzheimer disease (AD) in vivo. METHODS: Thirty-two patients with moderate AD were divided into carriers and noncarriers of the epsilon4 allele. These groups were matched for age, disease duration, education, and cognitive impairment. In all subjects, [11C]PIB-PET was performed for measurement of cerebral Abeta plaque deposition and cranial MRI for the assessment of gray matter volume by voxel-based morphometry (VBM) and for correction of partial volume effects (PVE) in the PET data. Voxel-based comparisons (SPM5) were performed between patient groups and healthy control populations and completed with multiple regression analyses between imaging data and epsilon4 allele frequency. RESULTS: Compared to controls, AD-typical patterns of [11C]PIB retention and atrophy were detected in both epsilon4-positive and epsilon4-negative patient groups. In direct comparison, significantly stronger and more extended [11C]PIB uptake was found in epsilon4-positive patients in bilateral temporoparietal and frontal cortex, surviving PVE correction. VBM analysis demonstrated comparable levels of atrophy in both patient groups. Regression analyses revealed a linear association between higher epsilon4 allele frequency and stronger temporoparietal Abeta plaque deposition, independently of other confounds. No major correlation between epsilon4 allele frequency and gray matter decrease was observed. CONCLUSION: These results indicate that the epsilon4-positive APOE genotype not only represents a risk factor for Alzheimer disease (AD), but also results in higher levels of Abeta plaque deposition in epsilon4-positive patients with AD compared to age-matched epsilon4-negative patients with similar levels of cognitive impairment and brain atrophy. The potential role of Abeta plaque imaging for patient inclusion and follow-up in anti-amyloid therapy trials is strengthened by these findings.
Authors:
A Drzezga; T Grimmer; G Henriksen; M Mühlau; R Perneczky; I Miederer; C Praus; C Sorg; A Wohlschläger; M Riemenschneider; H J Wester; H Foerstl; M Schwaiger; A Kurz
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-01
Journal Detail:
Title:  Neurology     Volume:  72     ISSN:  1526-632X     ISO Abbreviation:  Neurology     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-28     Completed Date:  2009-06-23     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0401060     Medline TA:  Neurology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1487-94     Citation Subset:  AIM; IM    
Affiliation:
Department of Nuclear Medicine, Klinikum Rechts der Isar, Technischen Universität München, Ismaninger Str. 22, D-81675 München/Munich, Germany. a.drzezga@lrz.tum.de
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Alzheimer Disease / genetics*,  pathology*,  radionuclide imaging
Amyloid beta-Protein / metabolism
Apolipoprotein E4 / genetics
Apolipoproteins E / genetics*
Benzothiazoles / diagnostic use
Brain / metabolism,  pathology*,  radionuclide imaging
Carbon Radioisotopes
DNA Mutational Analysis
Female
Gene Frequency / genetics
Genetic Predisposition to Disease / genetics
Genetic Testing
Genotype
Humans
Male
Middle Aged
Polymorphism, Genetic / genetics*
Positron-Emission Tomography
Risk Factors
Senile Plaques / metabolism,  pathology*
Chemical
Reg. No./Substance:
0/Amyloid beta-Protein; 0/Apolipoprotein E4; 0/Apolipoproteins E; 0/Benzothiazoles; 0/Carbon Radioisotopes; 0/N-methyl-2-(4'-methylaminophenyl)-6-hydroxybenzothiazole

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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