Apolipoprotein E and viral infection: Risks and Mechanisms

Chen, Feng; Ke, Qiongwei; Wei, Wenqing; Cui, Lili; Wang, Yan

doi:10.1016/j.omtn.2023.07.031

Cited by 14 publications

(6 citation statements)

References 143 publications

(172 reference statements)

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“…Recently, the emerging relationship between APOE and viral infection has been reported (Chen et al, 2023). So, our study, five infection types were considered along with APOE4 for regression analysis: infections (Table 1), acute infections, Influenza and Pneumonia, herpesviral infections, and Mycoses (Supplementary material, Infection types; Supplementary Tables 17, 18).…”

Section: Infections and Apoementioning

confidence: 99%

Prior infections are associated with smaller hippocampal volume in older women

Popov,

Ukraintseva,

Duan

et al. 2024

Front. Dement.

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Accumulating evidence suggests that infections may play a major role in Alzheimer's disease (AD), however, mechanism is unclear, as multiple pathways may be involved. One possibility is that infections could contribute to neurodegeneration directly by promoting neuronal death. We explored relationships between history of infections and brain hippocampal volume (HV), a major biomarker of neurodegeneration, in a subsample of the UK Biobank (UKB) participants. Infectious disease diagnoses were based on ICD10 codes. The left/right HV was measured by the magnetic resonance imaging (MRI) in cubic millimeters and normalized. Analysis of variance (ANOVA), Welch test, and regression were used to examine statistical significance. We found that HV was significantly lower in women aged 60–75, as well as 65–80, years, with history of infections, compared to same age women without such history. The effect size increased with age faster for the left vs. right HV. Results for males didn't reach statistical significance. Results of our study support a major role of adult infections in neurodegeneration in women. The detrimental effect of infections on HV became stronger with age, in line with declining resilience and increasing brain vulnerability to stressors due to aging. The faster increase in the effect size observed for the left vs. right HV may indicate that female verbal memory degrades faster over time than visual-spatial memory. The observed sex difference may reflect a higher vulnerability of female brain to infection-related factors, which in turn may contribute to a higher risk of AD in women compared to men.

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Section: Infections and Apoementioning

confidence: 99%

Prior infections are associated with smaller hippocampal volume in older women

Popov,

Ukraintseva,

Duan

et al. 2024

Front. Dement.

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“…Apolipoprotein E (apoE), an integral lipid-carrying protein in plasma, governs the transformation and metabolism of lipoproteins. 1 The apoE e4 gene, a variant of apoE, has emerged as a pivotal genetic factor for Alzheimer's disease (AD), increasing the risk among carriers. 2,3 This link underscores the need for accurate, sensitive, and efficient apoE gene detection methods.…”

Section: Introductionmentioning

confidence: 99%

Dual-mode fluorescence and electrochemiluminescence sensors based on Ru-MOF nanosheets for sensitive detection of apoE genes

Hu,

Cui,

Yin

et al. 2024

J. Mater. Chem. B

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“…The APOE gene encodes the glycoprotein apolipoprotein E (apoE), which has essential roles in lipid metabolism and impacts on many biological processes, including immune function (2). There are three main APOE alleles -ε2, ε3, and ε4 -defined by genotypes at two genetic variants, and resulting in different amino acids within mature ApoE at residues 112 and 158 (3). These amino acids affect the structure and function of the protein, including receptor binding, affinities for lipoproteins, and stability, as well as disease risk.…”

mentioning

confidence: 99%

“…Since several infections have been associated with AD (5), and some evidence additionally suggests that APOE genotype may affect susceptibility to or severity of viral infections (3), it is possible the effects of APOE on AD risk may be partly mediated through infection status or immunological response. Increased risks of HSV-1, human immunodeficiency virus, and SARS-CoV-2 infection and/or severe outcomes have been reported among ε4 carriers; and risk of seropositivity to hepatitis B and C may be higher among non-ε4 carriers (3,6). While evidence has been conflicting, suggested pathways include different affinities of apoE isoforms for receptors also involved in pathogen entry, such as heparin sulphate proteoglycans and lowdensity lipoprotein receptors (3,7).…”

mentioning

confidence: 99%

“…Increased risks of HSV-1, human immunodeficiency virus, and SARS-CoV-2 infection and/or severe outcomes have been reported among ε4 carriers; and risk of seropositivity to hepatitis B and C may be higher among non-ε4 carriers (3,6). While evidence has been conflicting, suggested pathways include different affinities of apoE isoforms for receptors also involved in pathogen entry, such as heparin sulphate proteoglycans and lowdensity lipoprotein receptors (3,7). However, these studies have been small and investigated few pathogens in parallel, with limited control for confounding.…”

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confidence: 99%

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No clear evidence for relationships of Apolipoprotein E genotype with measures of common infections in three UK cohorts

Green,

Fernández-Sanlés,

Felici

et al. 2024

Preprint

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APOEgenotype is the strongest genetic risk factor for late onset Alzheimer's disease, with the ϵ2 and ϵ4 alleles decreasing and increasing risk relative to the ϵ3 allele, respectively. Although evidence has been conflicting, several common infections have been associated with Alzheimer's disease risk, and interactions byAPOEϵ4 carriage have also been reported. Nevertheless, to date, no study has examined relationships betweenAPOEgenotype and measures of multiple common infections among large population-based studies. We investigated associations ofAPOEϵ2 and ϵ4 carriage (i.e. non-carrier vs carrier) with serostatus and antibody titers to 14 common pathogens — encompassing herpesviruses, human polyomaviruses,C.trachomatis,H.pylori, andT.gondii— in three population—based cohorts (UK Biobank, National Survey of Health and Development, Southall and Brent Revisited). Pathogen serostatus was derived using validated antibody cut-offs for relevant antigens and included as an outcome assessing previous infection. Antibody titers were dichotomised among the seropositive subset for each antigen and included as binary outcomes assessing recent immunological responses. We conducted analyses in each cohort using mixed-models, including age, sex and genetic principal components as fixed-effects, and genetic relatedness as a random-effect. In secondary analyses, we additionally assessed i) relationships ofAPOEϵ2 and ϵ4 dosage (i.e. number of copies of the allele of interest), and ii) relationships ofAPOEgenotype with continuous antibody titers (rank-based inverse normal transformed). Findings were meta-analysed across cohorts (n=10,059) using random-effects models and corrected for multiple tests using the false discovery rate. We found no clear evidence of relationships betweenAPOEgenotype and serostatus or antibody titers to any pathogen, with no strong associations observed in any of our analyses following multiple testing correction. Investigations ofAPOEgenotypes with the clinical manifestations of these pathogens, as well as expanding to include other viruses such as SARS-CoV-2, would also be warranted.

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Apolipoprotein E and viral infection: Risks and Mechanisms

Cited by 14 publications

References 143 publications

Prior infections are associated with smaller hippocampal volume in older women

Prior infections are associated with smaller hippocampal volume in older women

Dual-mode fluorescence and electrochemiluminescence sensors based on Ru-MOF nanosheets for sensitive detection of apoE genes

No clear evidence for relationships of Apolipoprotein E genotype with measures of common infections in three UK cohorts

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