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

Wu, Lingli; Du, Chao; Xu, Kai; Sun, Jinping; Zhang, Junying; Li, He; Li, Xin

doi:10.3389/fnagi.2020.00183

Cited by 3 publications

(1 citation statement)

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“…Resting-state functional magnetic resonance imaging (rs-fMRI) has become a reliable tool for studying brain function (Biswal et al, 1995;Fox and Raichle, 2007). Zhang et al (2020) found that T/T carriers showed an accelerated agerelated increase in functional activation in the left postcentral gyrus compared with G-allele carriers, which demonstrate that the rs405509 T/T allele of APOE causes an age-related brain functional decline in nondemented elderly people. Ma et al (2016a) found that the APOE-rs405509 interaction impairs elderly's cognitive performance through brain functional network.…”

Section: Introductionmentioning

confidence: 99%

The Effects of rs405509 on APOEε4 Non-carriers in Non-demented Aging

Zhao

et al. 2021

Front. Neurosci.

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BackgroundThere is evidence that the T allele of rs405509 located in the apolipoprotein E (APOE) promotor region is a risk factor for Alzheimer’s disease (AD). However, the effect of the T/T allele on brain function in non-demented aging is still unclear.MethodsWe analyzed the effects of the rs405509 T/T allele on cognitive performances using multiple neuropsychological tests and local brain function using resting-state functional magnetic resonance imaging (rs-fMRI).ResultsSignificant differences were found between T/T carriers and G allele carriers on general cognitive status, memory, and attention (p < 0.05). Rs-fMRI analyses demonstrated decreased amplitude of low frequency fluctuation (ALFF) in the right middle frontal gyrus, decreased percent amplitude of fluctuation (PerAF) in the right middle frontal gyrus, increased regional homogeneity (ReHo) in the right cerebellar tonsil and decreased ReHo in the right putamen, and decreased degree centrality (DC) in the left middle frontal gyrus (p < 0.05, corrected). Furthermore, significant correlations were found between cognitive performance and these neuroimaging changes (p < 0.05).ConclusionThese findings suggest that T/T allele may serve as an independent risk factor that can influence brain function in different regions in non-demented aging.

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Section: Introductionmentioning

confidence: 99%

The Effects of rs405509 on APOEε4 Non-carriers in Non-demented Aging

Zhao

et al. 2021

Front. Neurosci.

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The impact of APOE and smoking history on cognitive function in older, long-term breast cancer survivors

et al. 2022

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To determine whether older breast cancer survivors score lower on neuropsychological tests compared to matched non-cancer controls and to test the hypotheses that survivors who were APOE ε4 carriers would have the lowest cognitive performance, but that smoking history would decrease the negative effect of ε4 on cognition. MethodsFemale breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5 -15 year survivors (N=328) and age and education matched non-cancer controls (N=160) were assessed at enrollment and at 8, 16 and 24 month follow ups with standard neuropsychological and psychological assessments. Blood for APOE genotyping was collected and smoking history was assessed at enrollment. Participants were purposely recruited so that approximately 50% had a history of treatment with chemotherapy or no chemotherapy and approximately 50% had a smoking history. ResultsAfter adjusting for age, cognitive reserve, depression and fatigue, breast cancer survivors scored signi cantly lower on all domains of cognitive function. A signi cant two-way interaction demonstrated that the negative effect of ε4 on cognitive performance was stronger among survivors. A signi cant three-way interaction supported the hypothesis that smoking history had a protective effect on cognitive function in ε4 carriers that was more pronounced in the controls than the survivors. ConclusionsThe results support the long-term cognitive impact of breast cancer diagnosis and treatments on older, disease-free survivors, particularly for ε4 carriers. The results also emphasize the importance of assessing smoking history when examining APOE and cognition and are an example of the complex interactions of age, genetics, health behaviors and disease history in determining cognitive function.

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The Contributions of the Endolysosomal Compartment and Autophagy to APOE ɛ4 Allele-Mediated Increase in Alzheimer’s Disease Risk

Asiamah,

Feng,

Guo

et al. 2024

JAD

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Apolipoprotein E4 (APOE4), although yet-to-be fully understood, increases the risk and lowers the age of onset of Alzheimer’s disease (AD), which is the major cause of dementia among elderly individuals. The endosome-lysosome and autophagy pathways, which are necessary for homeostasis in both neurons and glia, are dysregulated even in early AD. Nonetheless, the contributory roles of these pathways to developing AD-related pathologies in APOE4 individuals and models are unclear. Therefore, this review summarizes the dysregulations in the endosome-lysosome and autophagy pathways in APOE4 individuals and non-human models, and how these anomalies contribute to developing AD-relevant pathologies. The available literature suggests that APOE4 causes endosomal enlargement, increases endosomal acidification, impairs endosomal recycling, and downregulates exosome production. APOE4 impairs autophagy initiation and inhibits basal autophagy and autophagy flux. APOE4 promotes lysosome formation and trafficking and causes ApoE to accumulate in lysosomes. APOE4-mediated changes in the endosome, autophagosome and lysosome could promote AD-related features including Aβ accumulation, tau hyperphosphorylation, glial dysfunction, lipid dyshomeostasis, and synaptic defects. ApoE4 protein could mediate APOE4-mediated endosome-lysosome-autophagy changes. ApoE4 impairs vesicle recycling and endosome trafficking, impairs the synthesis of autophagy genes, resists being dissociated from its receptors and degradation, and forms a stable folding intermediate that could disrupt lysosome structure. Drugs such as molecular correctors that target ApoE4 molecular structure and enhance autophagy may ameliorate the endosome-lysosome-autophagy-mediated increase in AD risk in APOE4 individuals.

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

Cited by 3 publications

References 60 publications

The Effects of rs405509 on APOEε4 Non-carriers in Non-demented Aging

The Effects of rs405509 on APOEε4 Non-carriers in Non-demented Aging

The impact of APOE and smoking history on cognitive function in older, long-term breast cancer survivors

The Contributions of the Endolysosomal Compartment and Autophagy to APOE ɛ4 Allele-Mediated Increase in Alzheimer’s Disease Risk

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