The Apolipoprotein E ε4 Allele-Dependent Relationship Between Serum Lipid Levels and Cognitive Function: A Population-Based Cross-sectional Study

Shan, Wei; Gao, Ling; Jiang, Yu; Shang, Suhang; Chen, Chen; Dang, Liangjun; Huo, Kang; Wang, Jingyi; Qu, Qing

doi:10.3389/fnagi.2020.00044

Cited by 12 publications

(11 citation statements)

References 46 publications

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“…Cholesterol metabolism may also play an essential role in the pathophysiology of AD [ 14 ]. From human epidemiological studies, high levels of total cholesterol in serum could influence the processing of amyloid precursor protein (APP) in neurons, thereby increasing the risk for AD [ 15 , 16 , 17 ]. The activity of β- and γ-secretase complexes involved in APP cleavage depends on cholesterol metabolism [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease

Kaur

Seeger

Golovko

et al. 2021

IJMS

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Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment. It is hypothesized to develop due to the dysfunction of two major proteins, amyloid-β (Aβ) and microtubule-associated protein, tau. Evidence supports the involvement of cholesterol changes in both the generation and deposition of Aβ. This study was performed to better understand the role of liver cholesterol and bile acid metabolism in the pathophysiology of AD. We used male and female wild-type control (C57BL/6J) mice to compare to two well-characterized amyloidosis models of AD, APP/PS1, and AppNL-G-F. Both conjugated and unconjugated primary and secondary bile acids were quantified using UPLC-MS/MS from livers of control and AD mice. We also measured cholesterol and its metabolites and identified changes in levels of proteins associated with bile acid synthesis and signaling. We observed sex differences in liver cholesterol levels accompanied by differences in levels of synthesis intermediates and conjugated and unconjugated liver primary bile acids in both APP/PS1 and AppNL-G-F mice when compared to controls. Our data revealed fundamental deficiencies in cholesterol metabolism and bile acid synthesis in the livers of two different AD mouse lines. These findings strengthen the involvement of liver metabolism in the pathophysiology of AD.

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Section: Introductionmentioning

confidence: 99%

Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease

Kaur

Seeger

Golovko

et al. 2021

IJMS

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“…Another explanation could be the bias due to the lost follow-up of ε4 carriers due to CVD diseases in the high LDL-C group. Five among seven studies in a review detected no interaction between APOE ε4 and TC (Anstey et al, 2008), while some studies found the effect of cholesterol varied in APOE ε4 carriers and non-carriers (Hall et al, 2006;Wei et al, 2020). Possible explanations for the inconsistent results may be the differences in sample size, ethnicity, age, and other population characteristics.…”

Section: Discussionmentioning

confidence: 97%

“…A meta-analysis in 2007 pooling 72,150 participants from 22 studies demonstrated an obvious increase trend of TC and LDL-C in the order of APOE ε2ε2, ε2ε3, ε3ε3, ε3ε4, and ε4ε4 (Bennet et al, 2007). In the Chinese population, studies also found APOE ε2 carriers had lower TC and LDL-C than APOE ε2 non-carriers (Kang et al, 2016), and APOE ε4 carriers had higher serum TC, TG, and LDL levels and lower HDL levels than APOE ε4 non-carriers (Wei et al, 2020). In addition, age was also negatively associated with TC.…”

Section: Discussionmentioning

confidence: 98%

“…Some studies reported that increasing cholesterol was associated with AD risk only in ε4 non-carriers, not in ε4 carriers (Evans et al, 2000;Hall et al, 2006). In a Chinese population, low serum high-density lipoprotein cholesterol (HDL-C) levels had a higher risk for cognitive dysfunction only in ε4 carriers, while different types of cholesterol (TC, HDL-C, LDL-C, and triglycerides) were not associated with cognitive function in ε4 non-carriers (Wei et al, 2020). In contrast, some studies reported the effect of cholesterol on cognitive function was independent of APOE (Toro et al, 2014;An et al, 2019), and the high-cholesterol subgroup had a higher cognitive decline rate than the normalcholesterol subgroups with or without APOE ε4 (Evans et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Apolipoprotein E Induced Cognitive Dysfunction: Mediation Analysis of Lipids and Glucose Biomarkers in an Elderly Cohort Study

Liu

Iyer

et al. 2021

Front. Aging Neurosci.

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IntroductionPrior evidence suggested Apolipoprotein E (APOE), lipids, and glucose metabolism may act through the same pathways on the pathogenesis of Alzheimer’s disease (AD).MethodsThis prospective study used data from the Chinese Longitudinal Healthy Longevity Study. We tested the associations of APOE genotype (ε2ε2, ε2ε3, ε2ε4, ε3ε3, ε3ε4, and ε4ε4) and cognitive function using generalized estimating equations (GEE). We examined for possible mediation and effect modification by lipids and glucose level in this association.ResultsAPOE ε2 showed significant direct protective effect and indirect harmful effect through TC on cognitive function. Abnormal lipids or glucose levels were not consistently associated with cognitive dysfunction in our study. We did not detect significant indirect effects through lipids for APOE ε4 or any indirect effects through glucose.DiscussionThese findings suggested complicated relationships among APOE, lipids, glucose, and cognitive function. Further study can make validations in other populations.

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“…Also, peripheral serum levels of lipids have been associated with AD and cognitive impairment by an allele of APOE . However, emerging studies in mammals have suggested that specific alterations in fat profiles and even elevated fat storage can be associated with longevity [ 62 , 63 ].…”

Section: Protein Network Regulate Homeostasis To Influence Lifespanmentioning

confidence: 99%

A description of the relationship in healthy longevity and aging-related disease: from gene to protein

Wang

Gao

et al. 2021

Immun Ageing

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Human longevity is a complex phenotype influenced by both genetic and environmental factors. It is also known to be associated with various types of age-related diseases, such as Alzheimer’s disease (AD) and cardiovascular disease (CVD). The central dogma of molecular biology demonstrates the conversion of DNA to RNA to the encoded protein. These proteins interact to form complex cell signaling pathways, which perform various biological functions. With prolonged exposure to the environment, the in vivo homeostasis adapts to the changes, and finally, humans adopt the phenotype of longevity or aging-related diseases. In this review, we focus on two different states: longevity and aging-related diseases, including CVD and AD, to discuss the relationship between genetic characteristics, including gene variation, the level of gene expression, regulation of gene expression, the level of protein expression, both genetic and environmental influences and homeostasis based on these phenotypes shown in organisms.

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The Apolipoprotein E ε4 Allele-Dependent Relationship Between Serum Lipid Levels and Cognitive Function: A Population-Based Cross-sectional Study

Cited by 12 publications

References 46 publications

Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease

Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease

Apolipoprotein E Induced Cognitive Dysfunction: Mediation Analysis of Lipids and Glucose Biomarkers in an Elderly Cohort Study

A description of the relationship in healthy longevity and aging-related disease: from gene to protein

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