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Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
Effect of APOE genotype on amyloid plaque load and gray matter volume in Alzheimer disease
A Drzezga1, T Grimmer, G Henriksen
1Department of Nuclear Medicine, Klinikum Rechts der Isar, Technischen Universität München, Ismaninger Str. 22, D-81675 München/Munich, Germany. a.drzezga@lrz.tum.de
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.
Insights
The APOE epsilon4 allele in Alzheimer disease (AD) is linked to increased beta-amyloid (Abeta) plaque deposition. This study found higher Abeta plaque levels in epsilon4-positive AD patients compared to epsilon4-negative patients with similar atrophy.
Area of Science:
- Neuroscience
- Genetics
- Radiology
Background:
- Alzheimer disease (AD) is a neurodegenerative disorder characterized by beta-amyloid (Abeta) plaques.
- The apolipoprotein E (APOE) epsilon4 allele is a significant genetic risk factor for late-onset AD.
- The in vivo impact of APOE genotype on Abeta plaque load and brain atrophy in AD patients remains to be fully elucidated.
Purpose of the Study:
- To investigate the influence of the APOE epsilon4 allele on in vivo Abeta plaque deposition and brain atrophy in patients with Alzheimer disease.
- To compare Abeta plaque load and gray matter volume between AD patients who are carriers and non-carriers of the APOE epsilon4 allele.
Main Methods:
- Thirty-two patients with moderate Alzheimer disease (AD) were categorized into APOE epsilon4 allele carriers and non-carriers, matched for key demographic and clinical variables.
- [11C]PIB-PET imaging was used to quantify cerebral Abeta plaque deposition.
- Voxel-based morphometry (VBM) analysis of cranial MRI data assessed gray matter volume, with partial volume effect (PVE) correction applied to PET data.
Main Results:
- Both APOE epsilon4-positive and negative AD patients exhibited AD-typical patterns of [11C]PIB retention and atrophy compared to controls.
- Significantly higher and more widespread [11C]PIB uptake was observed in the temporoparietal and frontal cortex of epsilon4-positive AD patients, even after PVE correction.
- VBM analysis revealed comparable gray matter atrophy between the two patient groups, and regression analyses showed a linear association between epsilon4 allele frequency and temporoparietal Abeta deposition, independent of other factors.
Conclusions:
- The APOE epsilon4 genotype is associated with increased Abeta plaque deposition in Alzheimer disease patients.
- These findings reinforce the role of APOE epsilon4 as a risk factor for AD and highlight its impact on specific neuropathological features.
- Abeta plaque imaging may be valuable for patient selection and monitoring in anti-amyloid therapeutic trials for Alzheimer disease.
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