Is there a significant interaction effect between apolipoprotein E rs405509 T/T and ε4 genotypes on cognitive impairment and gray matter volume?

Ma, Chao; Zhang, Yan; Li, X.; Zhang, J.; Chen, K.; Liang, Ying; Chen, Y.; Liu, Z.; Zhang, Z.

doi:10.1111/ene.13052

Cited by 22 publications

(25 citation statements)

References 55 publications

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“…To that end, we are currently exploring the hypothesis that there is an association between either variant rs405509 (-219G/T) or rs769446 (-427T/C) and WMH development. These variants have been associated in the past with brain functional decline and may be a confounding factor in altitude-induced injury [ 14 , 15 ]. We anticipate developing a better understanding of ApoE ’s role in altitude-related negative effects through the currently reported results regarding ApoE status and the up-coming work on promoter genotypes.…”

Section: Main Textmentioning

confidence: 99%

Evaluating apolipoprotein E genotype status and neuroprotective effects against white matter hyperintensity development in high-altitude careers

Chapleau¹,

Martin²,

Hughes³

et al. 2018

BMC Res Notes

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ObjectiveThis study considers the use of a rapid molecular assay to evaluate apolipoprotein E (ApoE) status in military subjects who have been exposed to high altitude. We hypothesize that ApoE status may be protective against developing brain white matter hyperintensities (WMHs) after high altitude exposure.ResultsWe tested 92 subjects who had been exposed to altitudes above 25,000 ft mean sea level, either as pilots or as altitude chamber technicians. We determined subject genetic status using rapid Taqman-style polymerase chain reaction genotyping and evaluated the association of ApoE subtype versus brain lesions using t-tests and two-way analyses of variance. Our results indicate that there is no significant association between ApoE genotype status and the presence of WMHs after high altitude exposure. We did observe a significantly higher number of hours spent at altitude for subjects with the ApoE E2 allele; however, the mechanism by which this may occur is not determined in this study. To more fully elucidate this effect, larger populations would be required to observe greater numbers of subjects with the E2 and E4 alleles.

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Section: Main Textmentioning

confidence: 99%

Evaluating apolipoprotein E genotype status and neuroprotective effects against white matter hyperintensity development in high-altitude careers

Chapleau¹,

Martin²,

Hughes³

et al. 2018

BMC Res Notes

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“…Promoter polymorphisms may increase the dementia risk through the APOE4 pathway (Rantalainen et al, 2019 ), with expression levels of APOE4 determined by APOE promoter polymorphisms (Lescai et al, 2011 ). Previous studies have found that rs405509 T homozygosity can modulate the effect of APOE4 on both cognitive performance and brain structure (Ma et al, 2016a , b ). TT carriers with APOE4 suffered from a poor cognitive status and reduced GMV in the inferior temporal gyrus and fusiform gyrus, and more importantly, the cognitive and structural changes were significantly correlated (Ma et al, 2016b ).…”

Section: Discussionmentioning

confidence: 96%

“…Previous studies have found that rs405509 T homozygosity can modulate the effect of APOE4 on both cognitive performance and brain structure (Ma et al, 2016a,b). TT carriers with APOE4 suffered from a poor cognitive status and reduced GMV in the inferior temporal gyrus and fusiform gyrus, and more importantly, the cognitive and structural changes were significantly correlated (Ma et al, 2016b). This correlation may reflect the neuromechanism of gene interaction at the brain level and contribute to low cognitive function (Ma et al, 2016b).…”

Section: The Potential Pathological Mechanism Of Rs4055059 On Cognitimentioning

confidence: 99%

Effects of an APOE Promoter Polymorphism on Fronto-Parietal Functional Connectivity During Nondemented Aging

et al. 2020

Front. Aging Neurosci.

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Background: The rs405509 polymorphism of the apolipoprotein E (APOE) promoter is related to Alzheimer's disease (AD). The T/T allele of rs405509 is known to decrease the transcription of the APOE gene and lead to impairments in specific brain structural networks with aging; thus, it is an important risk factor for AD. However, it remains unknown whether rs405509 affects brain functional connectivity (FC) in aging. Methods: We investigated the effect of the rs405509 genotype (T/T vs. G-allele) on age-related brain FC using functional magnetic resonance imaging. Forty-five elderly TT carriers and 45 elderly G-allele carriers were scanned during a working memory (WM) task. Results: We found that TT carriers showed an accelerated age-related increase in functional activation in the left postcentral gyrus compared with G-allele carriers. Furthermore, the FC between the left postcentral gyrus and some key regions during WM performance, including the right caudal and superior frontal sulcus (SFS), was differentially modulated by age across rs405509 genotype groups. Conclusions: These results demonstrate that the rs405509 T/T allele of APOE causes an age-related brain functional decline in nondemented elderly people, which may be beneficial for understanding the neural mechanisms of rs405509-related cognitive aging and AD pathogenesis.

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“…Indeed, cognitive deficits are often thought to be associated with brain functional and/or structural impairments [ 28 , 29 ], which can be measured by using volumetric or functional magnetic resonance imaging (MRI) neuroimaging techniques. For example, resting state blood-oxygen-level dependent (BOLD) MRI allowed the delineation of the human neural functional architecture into multinetworks, such as the default mode network (DMN) and frontal-parietal network (FPN) [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

The Interactive Effects of Age and PICALM rs541458 Polymorphism on Cognitive Performance, Brain Structure, and Function in Non-demented Elderly

et al. 2017

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The PICALM rs541458 T allele has been recognized as a risk factor for late-onset Alzheimer’s disease, and age might modulate the effects that genetic factors have on cognitive functions and brain. Thus, the current study intended to examine whether the effects of rs541458 on cognitive functions, brain structure, and function were modulated by age in non-demented Chinese elderly. We enrolled 638 subjects aged 50 to 82 years and evaluated their cognitive functions through a series of neuropsychological tests. Seventy-eight of these participants also received T1-weighted structural and resting state functional magnetic resonance imaging. Dividing subjects into groups <65 and ≥65 years old, results of neuropsychological tests showed that interactive effects of rs541458 × age existed with regard to executive function and processing speed after controlling for gender, years of education and APOE ε4 status. In addition, the effects of rs541458 on resting state functional connectivity of left superior parietal gyrus within left frontal-parietal network and on gray matter volume of left middle temporal gyrus were modulated by age. Furthermore, reduction of functional connectivity of left superior parietal gyrus was closely related with better executive function in the T allele carriers <65 years old. Further, greater volume of left middle temporal gyrus was significantly related to better executive function in both CC genotype <65 years old and CC genotype ≥65 years old groups, separately. Pending further confirmation from additional studies, our results support the hypothesis that the modulation of age, with respect to the rs541458, has interactional effects on cognitive performance, brain function, and structural measurements.Electronic supplementary materialThe online version of this article (doi:10.1007/s12035-016-0358-5) contains supplementary material, which is available to authorized users.

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Is there a significant interaction effect between apolipoprotein E rs405509 T/T and ε4 genotypes on cognitive impairment and gray matter volume?

Cited by 22 publications

References 55 publications

Evaluating apolipoprotein E genotype status and neuroprotective effects against white matter hyperintensity development in high-altitude careers

Evaluating apolipoprotein E genotype status and neuroprotective effects against white matter hyperintensity development in high-altitude careers

Effects of an APOE Promoter Polymorphism on Fronto-Parietal Functional Connectivity During Nondemented Aging

The Interactive Effects of Age and PICALM rs541458 Polymorphism on Cognitive Performance, Brain Structure, and Function in Non-demented Elderly

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