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Effect of APOE genotype on amyloid plaque load and gray matter volume in Alzheimer disease.
Neurology 2009; 72(17):1487-94Neur

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.

Authors+Show Affiliations

Department of Nuclear Medicine, Klinikum Rechts der Isar, Technischen Universität München, Ismaninger Str. 22, D-81675 München/Munich, Germany. a.drzezga@lrz.tum.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19339712

Citation

Drzezga, A, et al. "Effect of APOE Genotype On Amyloid Plaque Load and Gray Matter Volume in Alzheimer Disease." Neurology, vol. 72, no. 17, 2009, pp. 1487-94.
Drzezga A, Grimmer T, Henriksen G, et al. Effect of APOE genotype on amyloid plaque load and gray matter volume in Alzheimer disease. Neurology. 2009;72(17):1487-94.
Drzezga, A., Grimmer, T., Henriksen, G., Mühlau, M., Perneczky, R., Miederer, I., ... Kurz, A. (2009). Effect of APOE genotype on amyloid plaque load and gray matter volume in Alzheimer disease. Neurology, 72(17), pp. 1487-94. doi:10.1212/WNL.0b013e3181a2e8d0.
Drzezga A, et al. Effect of APOE Genotype On Amyloid Plaque Load and Gray Matter Volume in Alzheimer Disease. Neurology. 2009 Apr 28;72(17):1487-94. PubMed PMID: 19339712.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of APOE genotype on amyloid plaque load and gray matter volume in Alzheimer disease. AU - Drzezga,A, AU - Grimmer,T, AU - Henriksen,G, AU - Mühlau,M, AU - Perneczky,R, AU - Miederer,I, AU - Praus,C, AU - Sorg,C, AU - Wohlschläger,A, AU - Riemenschneider,M, AU - Wester,H J, AU - Foerstl,H, AU - Schwaiger,M, AU - Kurz,A, Y1 - 2009/04/01/ PY - 2009/4/3/entrez PY - 2009/4/3/pubmed PY - 2009/6/24/medline SP - 1487 EP - 94 JF - Neurology JO - Neurology VL - 72 IS - 17 N2 - 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. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/19339712/Effect_of_APOE_genotype_on_amyloid_plaque_load_and_gray_matter_volume_in_Alzheimer_disease_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=19339712 DB - PRIME DP - Unbound Medicine ER -