Effect of APOE genotype on amyloid plaque load and gray matter volume in Alzheimer disease  

Oleh:

Drzezga, A. ; Grimmer, T. ; Henriksen, G.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Neurology (Official Journal of The American Academy of Neurology) vol. 72 no. 17 (Apr. 2009), page 1487-1494.
Topik: MINI-MENTAL STATE EXAMINATION; SYNAPTIC DYSFUNCTION

Ketersediaan

Perpustakaan FK Nomor Panggil: N11.K.2009.03 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Objective: To examine the influence of the APOE genotype on levels of ß-amyloid (Aß) 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 {varepsilon}4 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 Aß 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 {varepsilon}4 allele frequency. Results: Compared to controls, AD-typical patterns of [11C]PIB retention and atrophy were detected in both {varepsilon}4-positive and {varepsilon}4-negative patient groups. In direct comparison, significantly stronger and more extended [11C]PIB uptake was found in {varepsilon}4-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 {varepsilon}4 allele frequency and stronger temporoparietal Aß plaque deposition, independently of other confounds. No major correlation between {varepsilon}4 allele frequency and gray matter decrease was observed. Conclusion: These results indicate that the {varepsilon}4-positive APOE genotype not only represents a risk factor for Alzheimer disease (AD), but also results in higher levels of Aß plaque deposition in {varepsilon}4-positive patients with AD compared to age-matched {varepsilon}4-negative patients with similar levels of cognitive impairment and brain atrophy. The potential role of Aß plaque imaging for patient inclusion and follow-up in anti-amyloid therapy trials is strengthened by these findings.

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