Sex Moderates the Effects of the Sorl1 Gene rs2070045 Polymorphism on Cognitive Impairment and Disruption of the Cingulum Integrity in Healthy Elderly

Liang, Ying; Li, He; Lv, Chen-Long; Shu, Ni; Chen, Kewei; Li, Xin; Zhang, Junying; Hu, Lina; Zhang, Zhanjun

doi:10.1038/npp.2015.1

Cited by 17 publications

(8 citation statements)

References 44 publications

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“…In addition to sex differences in APOE associations, sex interactions have also been observed among genes along the APOE signaling pathway including the sortilin related receptor 1 (SORL1) 39,40 which is a receptor for APOE, the ATP-binding cassette transporter 1 (ABCA1) 41 which is known to interact with APOE directly, 42 and the translocase of outer mitochondrial membrane 40 (TOMM40) gene which is located next to APOE and has not been disentangled from APOE effects (due to linkage disequilibrium) within a sex-specific context. 43 In all these cases, genetic variation was more robustly associated with clinical AD among females compared to males, reinforcing the importance of APOE signaling among females.…”

Section: Female-specific Genetic Associationsmentioning

confidence: 99%

Sex Differences in the Genetic Architecture of Alzheimer’s Disease

et al. 2019

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Purpose of Review.-Summarize sex-specific contributors to the genetic architecture of Alzheimer's disease (AD). Recent Findings.-There are sex differences in the effects of Apolipoprotein E (APOE), genes along the APOE pathway, and genes along the neurotrophic signaling pathway in predicting AD. Reported sex differences are largely driven by stronger associations among females. Evidence also suggests that genetic predictors of amyloidosis are largely shared across sexes, while sex-specific genetic effects emerge downstream of amyloidosis and drive the clinical manifestation of AD. Summary.-There is a lack of comprehensive assessments of sex differences in genome-wide analyses of AD and a need for more systematic reporting a sex-stratified genetic effects. The emerging emphasis on sex as a biological variable provides an opportunity for transdisciplinary collaborations aimed at addressing major analytical challenges that have hampered advancements in the field. Ultimately, sex-specific genetic association studies represent a logical first step towards precision medicine.

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Section: Female-specific Genetic Associationsmentioning

confidence: 99%

Sex Differences in the Genetic Architecture of Alzheimer’s Disease

et al. 2019

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“…In an attempt to better characterize the earliest white matter changes and their regional progression in the course of AD pathogenesis, recent DTI studies have more and more focused on asymptomatic at-risk populations, such as healthy subjects carrying AD-susceptibility genes, most notably the APOE4 allele (Bendlin et al, 2010; Kljajevic et al, 2014; Westlye, Reinvang, Rootwelt, & Espeseth, 2012; Xiong et al, 2011), but also other risk-associated candidate genes (Braskie et al, 2012, 2011; Forde et al, 2014; Liang, Li, et al, 2015; Lyall et al, 2014; Voineskos et al, 2011), or completely dominant familial AD mutations (Ringman et al, 2007; Ryan et al, 2013). Other recent studies examined white matter changes in asymptomatic individuals showing biomarker evidence of amyloid or tau pathology (Bendlin et al, 2012; Chao et al, 2013; Gold et al, 2014; Kantarci et al, 2014; Molinuevo et al, 2014; Racine et al, 2014; Stenset et al, 2011).…”

Section: Contribution Of Cortical Disconnection To Ad Phenotype and Dmentioning

confidence: 99%

Measuring Cortical Connectivity in Alzheimer’s Disease as a Brain Neural Network Pathology: Toward Clinical Applications

Teipel

Grothe

Zhou

et al. 2016

J Int Neuropsychol Soc

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Objectives: The objective was to review the literature on diffusion tensor imaging as well as resting-state functional magnetic resonance imaging and electroencephalography (EEG) to unveil neuroanatomical and neurophysiological substrates of Alzheimer's disease (AD) as a brain neural network pathology affecting structural and functional cortical connectivity underlying human cognition. Methods: We reviewed papers registered in PubMed and other scientific repositories on the use of these techniques in amnesic mild cognitive impairment (MCI) and clinically mild AD dementia patients compared to cognitively intact elderly individuals (Controls). Results: Hundreds of peer-reviewed (cross-sectional and longitudinal) papers have shown in patients with MCI and mild AD compared to Controls (1) impairment of callosal (splenium), thalamic, and anterior-posterior white matter bundles; (2) reduced correlation of resting state blood oxygen level-dependent activity across several intrinsic brain circuits including default mode and attention-related networks; and (3) abnormal power and functional coupling of resting state cortical EEG rhythms. Clinical applications of these measures are still limited. Conclusions: Structural and functional (in vivo) cortical connectivity measures represent a reliable marker of cerebral reserve capacity and should be used to predict and monitor the evolution of AD and its relative impact on cognitive domains in pre-clinical, prodromal, and dementia stages of AD. (JINS, 2016, 22, 138-163)

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“…Here we chose some candidate risk SNPs of AD including APOE (genotypes with 2 SNPs: rs429358 and rs7412), TOMM40 (rs2075650), SORL1 (rs2070045) and APOE promoter polymorphisms − 219 (rs405509), with the evidence to be associated with increased risk of dementia and cognitive impairment in Chinese elderly [11,12]. For aspects of cognitive function, the de cit of memory is a typical characteristic of people with cognitive impairment, in the transitional stage between normal aging and dementia, especially episodic memory [13,14].…”

Section: Introductionmentioning

confidence: 99%

Effects of Cognitive- and Sleep- Related Single Nucleotide Polymorphisms on Cognitive Functions in the Han Chinese Community-dwelling Elderly

Zheng

et al. 2020

Preprint

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Objective: The genetic biomarkers on Alzheimer’s disease (AD) have been widely studied in different groups. Since the lack of efficacy therapeutic methods for AD, early recognition in preclinical stage becomes increasingly important. Evidence of AD and cognitive-related single nucleotide polymorphisms (SNPs) in high risk population is insufficiency. Our aim was to assess whether these SNPs within cognitive- and sleep- associated genes are correlated with cognitive impairment independently or through gene-gene interactions in community-dwelling elderly in Beijing. Methods: Eight single-nucleotide polymorphisms (SNPs) were genotyped in 2133 Northen Han Chinese elderly from ten communites in Chaoyang District, Beijing. The short version of the Montreal Cognitive Assessment-Beijing (MoCA-s), Ascertain Dementia 8 (AD8), Digit Span Backwards (DSB), Digital Symbol Substitution Test (DSST), and Paired Associative Learning Test (PALT) were used to detect different cognitive domains.Results: Logistic regression analyses showed a significant correlation between APOE (rs429358), ABCC9 (rs11046205) and cognitive impairment, and an interaction between ABCC9 (rs11046205)/APOE promoter (rs405509) and APOE ε4 status. Additionally, we found a significant negative association between the additive model of APOE (rs429358) and MMSE score. Moreover, our analysis revealed that the gene-gene interaction between ABCC9 (rs11046205) and APOE (429358) may contribute to the etiology of congnitive impairment.Conclusions: This study confirmed the independent contribution of AD, memory and sleep-related genes in the cognitive impairment of the community-dwelling elderly in China, as well as through gene-gene interactions.

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Sex Moderates the Effects of the Sorl1 Gene rs2070045 Polymorphism on Cognitive Impairment and Disruption of the Cingulum Integrity in Healthy Elderly

Abstract: In this article, the third author, Chenlong Lv, is affiliated only to affiliations number 4 and 6.6 These authors contributed equally to this work.

Cited by 17 publications

References 44 publications

Sex Differences in the Genetic Architecture of Alzheimer’s Disease

Sex Differences in the Genetic Architecture of Alzheimer’s Disease

Measuring Cortical Connectivity in Alzheimer’s Disease as a Brain Neural Network Pathology: Toward Clinical Applications

Effects of Cognitive- and Sleep- Related Single Nucleotide Polymorphisms on Cognitive Functions in the Han Chinese Community-dwelling Elderly

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