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Effect of APOE genotype on amyloid plaque load and gray matter volume in Alzheimer disease
Abstract
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.
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“Plaque deposition is increased with APOE4 compared with APOE2 and APOE3 in humans and transgenic mice expressing familial AD (FAD) mutations (FAD-Tg) (2)(3)(4)(5).”
From APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease (2012) · cites this paper as [4]
In the citing paper
“The primary genetic risk factor for Alzheimer disease (AD) 4 is APOE4, increasing the risk by ϳ4and 15-fold with a single or double allele, whereas APOE2 reduces the risk compared with APOE3.”
From APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease (2012) · cites this paper as [4]
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Metadata
- Authors
- Drzezga, A., Grimmer, T., Henriksen, G., Mühlau, M., Perneczky, R., Miederer, I., Praus, C., Sorg, C., Wohlschläger, A., Riemenschneider, M., Wester, H. J., Foerstl, H., Schwaiger, M., & Kurz, A.
- Affiliations
- Technical University of Munich (DE)
- From the Departments of Nuclear Medicine (A.D., G.H., I.M., C.P., A.W., H.J.W., M.S.), Psychiatry and Psychotherapy (T.G., R.P., C.S., M.R., H.F., A.K.), Neurology (M.M.), and Neuroradiology (A.W.), Technische Universität München, Munich, Germany.
- ORCID
- Venue
- Neurology
- Published
- 2009-04-28
- Volume
- 72
- Issue
- 17
- Pages
- 1487-1494
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2050255138
- Cited by
- 248
- References
- 38
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 7 · 2023: 4 · 2022: 16 · 2021: 6 · 2020: 8 · 2019: 9 · 2018: 17 · 2017: 13 · 2016: 16 · 2015: 18 · 2014: 22 · 2013: 15 · 2012: 25
- FWCI
- 18.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- APOE ε4, Alzheimer's disease, amyloid plaques, gray matter atrophy, 11C-PiB PET, amyloid imaging, genetic risk factors, temporoparietal cortex, partial volume correction
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Aniline Compounds, Apolipoproteins E, Brain, Carbon Radioisotopes, DNA Mutational Analysis, Female, Gene Frequency, Genetic Testing, Genotype, Humans, Male, Middle Aged, Polymorphism, Genetic, Risk Factors, Thiazoles, Amyloid beta-Peptides, Genetic Predisposition to Disease, Positron-Emission Tomography, Benzothiazoles, Apolipoprotein E4, Plaque, Amyloid
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