Modulation on brain gray matter activity and white matter integrity by APOE ε4 risk gene in cognitively intact elderly: A multimodal neuroimaging study

Cai, Suping; Jiang, Yuanyuan; Wang, Yübo; Wu, Xiaoming; Ren, Junchan; Lee, Min Seob; Lee, Sung-Hoon

doi:10.1016/j.bbr.2017.01.027

Cited by 16 publications

(16 citation statements)

References 67 publications

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“…AD non-carriers: ↓ FA in left medial temporal areas, parahippocampal cingulum, bilateral intracalcarine sulcus, precuneus, lingual area • Healthy carriers vs. healthy non-carriers: ↓ FA bilateral medial temporal areas, scattered regions in frontal & parietal lobes & cerebellum Bendlin et al, 2010 136 (56; 80) 69.2 (10.2) VBA 3 0 2 × 2 × 3 12 1 Whole brain • Carriers vs. non-carriers: no significant differences Brown et al, 2011 55 (25; 30) 62.3 (9.0) Structural connectivity 3 800 or 1000 2.5 × 2.5 × 2.5 30 1 Global & regional connectivity • Carriers vs. non-carriers: age-related loss of mean local interconnectivity, & regional local interconnectivity decreases in the precuneus, medial orbitofrontal cortex, & lateral parietal cortex. Cai et al, 2017 309 (116; 193) 73.9 (4.6) VBA 3 Not reported 1.02 × 1.02 × 1.02 Not reported 1 Superior corona radiata, genu of corpus callosum • Carriers vs. non-carriers: ↑ MD in superior corona radiata, genu of corpus callosum. No significant associations with FA or RD Cavedo et al, 2017 74 (31; 43) across 4 centres 68.9 (6.9) TBSS, VBA 1.5 or 3 0, 1000 or 0, 800 2 × 2 × 2 or 1 × 1 × 2.4 12, 15, 20 or 60 1 Whole brain • Carriers vs. non-carriers: ↓ FA globally, and in genu, body & splenium of corpus callosum, internal capsule, external capsule, inferior fronto-occipital & inferior longitudinal fasciculi, cingulum (left & right).…”

Section: Resultsmentioning

confidence: 99%

Imaging Alzheimer's genetic risk using diffusion MRI: A systematic review

Harrison

Bhatia

Tan

et al. 2020

NeuroImage: Clinical

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Highlights dMRI uses the movement of water molecules to quantify white matter microstructure. dMRI has demonstrated changes in white matter microstructure in Alzheimer’s Disease. We provide a systematic review of 37 dMRI studies of Alzheimer’s genetic risk. Alzheimer’s risk genes were linked to decreased anisotropy and greater diffusivity. Signal changes are non-specific, and the field faces several methodological challenges.

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Section: Resultsmentioning

confidence: 99%

Imaging Alzheimer's genetic risk using diffusion MRI: A systematic review

Harrison

Bhatia

Tan

et al. 2020

NeuroImage: Clinical

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“…It is dedicated to investigating the distinct connectivity within the DMN that could represent the progressive biomarker. However, the results of resting state functional MRI (rs-fMRI) ( Teipel et al, 2015 ) and APOE studies have reported mixed results ( Cai et al, 2017 ; Luo et al, 2017 ; Caldwell et al, 2019 ; Zhu et al, 2019 ). Some reported decreased functional connectivity ( Yan et al, 2015 ) in APOE e4 allele carriers (APOE4+) compared with non-carries (APOE4-), the others found some increased functional connectivity ( Song et al, 2015 ; Zhu et al, 2018 ), while others didn’t found any differences ( Chiesa et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Default Mode Network Analysis of APOE Genotype in Cognitively Unimpaired Subjects Based on Persistent Homology

Kuang

Jia

Zhao

et al. 2020

Front. Aging Neurosci.

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Current researches on default mode network (DMN) in normal elderly have mainly focused on finding some dysfunctional areas with decreased or increased connectivity. The global network dynamics of apolipoprotein E (APOE) e4 allele group is rarely studied. In our previous brain network study, we have demonstrated the advantage of persistent homology. It can distinguish robust and noisy topological features over multiscale nested networks, and the derived properties are more stable. In this study, for the first time we applied persistent homology to analyze APOE-related effects on whole-brain functional network. In our experiments, the risk allele group exhibited lower network radius and modularity in whole brain DMN based on graph theory, suggesting the abnormal organization structure. Moreover, two suggested measures from persistent homology detected significant differences between groups within the left hemisphere and in the whole brain in two datasets. They were more statistically sensitive to APOE genotypic differences than standard graph-based measures. In summary, we provide evidence that the e4 genotype leads to distinct DMN functional alterations in the early phases of Alzheimer’s disease using persistent homology approach. Our study offers a novel insight to explore potential biomarkers in healthy elderly populations carrying APOE e4 allele.

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“…A working solution (4.4 µmol/l) of Fluo-3/acetoxymethyl ester dry powder (DingGuo Biotech Co., Ltd., Beijing, China) in anhydrous dimethyl sulfoxide was prepared, according to the method described in a previous study ( 16 ). Briefly, at 12, 24, 48 and 72 h after introducing the scratches, astrocytes in the dishes were rinsed with Hank's solution (Sigma-Aldrich, Merck KGaA, Darmstadt, Germany), treated with ~1 ml Fluo-3 working solution and placed in an incubator at 37°C, ensuring that the cells were protected from light, in order to load the cells with fluorescent probe for 45 min.…”

Section: Methodsmentioning

confidence: 99%

Effects of apolipoprotein E gene polymorphism on the intracellular Ca2+ concentration of astrocytes in the early stages post injury

Zhou

Zhao

et al. 2017

Exp Ther Med

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The present study aimed to investigate the correlation between apolipoprotein E (APOE) polymorphisms and the intracellular concentration of Ca2+ in astrocytes in the early stages after an injury. The chondroitin sulfate region of three APOE alleles (ε2, ε3 and ε4) was obtained by reverse transcription-polymerase chain reaction (RT-PCR). A recombinant plasmid, pEGFP-N1-APOE, was constructed and identified by sequencing, while astrocytes were isolated from APOE gene-knockout mice and examined using immunocytochemistry. The recombinant plasmid was transfected into the astrocytes using the liposome-mediated method and cell injury models were constructed by a scratch assay. Laser confocal scanning microscopy (LCSM) was used to detect dynamic alterations in intracellular Ca2+ concentration at 12, 24, 48 and 72 h after injury. Compared with the control group, cells transfected with any of the three alleles demonstrated significant increases in the fluorescence intensity of Ca2+ (P<0.05). The fluorescence intensity of Ca2+ was weak at 12 h after injury, with no statistically significant difference detected between any two groups at this time point (P>0.05). However, the fluorescence intensity increased in a time-dependent manner and at 24, 48 and 72 h post injury, the fluorescence intensity of the ε4 allele-containing cells was significantly higher when compared with that of cells harboring the other two alleles (P<0.05). These results indicate that intracellular Ca2+ overloading may contribute to the deterioration of brain cells and poor outcome subsequent to traumatic brain injury in APOE ε4 carriers.

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Modulation on brain gray matter activity and white matter integrity by APOE ε4 risk gene in cognitively intact elderly: A multimodal neuroimaging study

Cited by 16 publications

References 67 publications

Imaging Alzheimer's genetic risk using diffusion MRI: A systematic review

Imaging Alzheimer's genetic risk using diffusion MRI: A systematic review

Default Mode Network Analysis of APOE Genotype in Cognitively Unimpaired Subjects Based on Persistent Homology

Effects of apolipoprotein E gene polymorphism on the intracellular Ca2+ concentration of astrocytes in the early stages post injury

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