Apolipoprotein E Gene Research Articles

Association between Apolipoprotein E gene polymorphism and early MR findings in individuals with acute intracerebral hemorrhage: a retrospective cohort analysis

ObjectiveThe Apolipoprotein E (APOE) gene plays a significant role in the development and prognosis of intracerebral hemorrhage (ICH). Imaging features identified within 48 hours of ICH onset, particularly on magnetic resonance imaging (MRI), are indicative of cerebral small vessel diseases (CSVD). Our study aimed to assess these imaging characteristics and investigate their association with the APOE gene among ICH patients. MethodsClinical and imaging data from patients meeting specific inclusion and exclusion criteria from October 2021 to March 2022 were collected. MR signs or scores were evaluated following international accreditation standards and then analyzed in connection with the APOE allele genes. ResultsIn a cohort of 220 patients, ε2 was identified as an independent risk factor for the "multiple subcortical spots" sign (OR = 13.29, 95% CI 1.88-22.59). Furthermore, ε4 emerged as an independent risk factor for the presence of perivascular space (PVS) in the centrum semiovale (OR = 2.46, 95% CI 1.03-5.89) and basal ganglia (OR = 2.64, 95% CI 1.10-6.35), as well as for cerebral microbleeds (CMB) across all locations (OR = 2.38, 95% CI 1.15-6.97), lobar CMB (OR = 2.92, 95% CI 1.11-7.65), and deep CMB (OR = 2.29, 95% CI 1.12-8.67). ConclusionThe association between APOE ɛ2 and ɛ4 alleles and the presence of "subcortical multiple spots," "PVS," and "CMB" indirectly implies the potential role of APOE gene-related pathological changes in the progression of ICH and small vessel pathology.

PPAR-γ Signaling and Common Protective Pathways against Obesity and Alzheimer's Disease

Transcription factor PPAR-γ is predominantly found in adipose tissue, liver, and brain. PPARs form heterodimers, interact with ligands, and regulate the expression of the genes of the PPAR-γ downstream regulatory pathways. PPAR-γ is critical in regulating many physiological processes, including adipogenesis, glucose metabolism, fatty acid metabolism, energy homeostasis, and inflammation. This review is on the functions of PPAR-γ and how dysregulation of activity or expression of PPAR-γ can lead to obesity and Alzheimer's disease (AD). The PPAR- γ agonist inhibited the downregulated pathways, such as Wnt/β-Catenin and JAK-STAT pathways, both involved in activating NF-kB. PPAR-γ has a significant role in the APOE (Apolipoprotein E) gene expression, which reduces reducing obesity, inhibits amyloid aggregation, prevents hyperphosphorylation of tau, and inhibits dysregulation of autophagy. This review provides a perspective on the intricate interplay between PPAR-γ, obesity, and AD, focusing on the molecular mechanisms and potential therapeutic implications.

Sex Differences in Cortical Thickness and Neuropsychiatric Symptom Burden Based on APOE4 Homozygosity in Alzheimer's Disease.

Sex differences in patterns of cortical thickness and neuropsychiatric symptom (NPS) burden were examined among individuals with Alzheimer's disease (AD) and two copies (homozygote carriers) of the e4 allele of the apolipoprotein gene (APOE). A total of 752 participants with a clinical etiologic diagnosis of AD were selected from the National Alzheimer's Coordinating Center (NACC) database. Bayesian multilevel regression was used to examine both the within- and between-sex differences in gray-matter cortical thickness and total NPS burden associated with APOE homozygosity. Female homozygote carriers displayed a high probability of having reduced cortical thickness primarily in medial-lateral temporal regions and a greater burden of NPS, relative to both non-homozygous females and homozygous males. These findings support the notion that APOE4 status affects cortical thickness and symptom burden in men and women with AD differentially, with females showing more pronounced effects in brain areas known to be vulnerable in early AD. Future investigations should attempt to elucidate the proposed pattern of decline longitudinally.

Association of apolipoprotein E gene polymorphism with gallstone disease in Iraqi Kurdish women

Gallstone disease (GSD) is a worldwide problem; the frequency of GSD varies greatly amongst different ethnic groups, possibly due to environmental and genetic factors. One circulating lipoprotein involved in lipid metabolism is apolipoprotein E (APOE). The APOE gene is polymorphic, has three distinct alleles, APOE2, APOE3, and APOE4. The an APOE polymorphism is linked to a variety of diseases, including Alzheimer's and type-two diabetes, so this study aimed to assess the relationship among various APOE genotypes and alleles with gallstone cases in Iraqi Kurdish women. The present case-control study involved 81 cases with laparoscopic cholecystectomy for gallstone disease and 80 healthy women without GSD. Genomic DNA samples were taken from blood to find the genotype of APOE using allele-specific sequence-primers and a method based on polymerase chain reaction (PCR). lipid profiles were examined using an automated biochemical analyzer. SPSS and GraphPad Prism 9.1.1 software were used to conduct the statistical analysis. No significant relationships were found between healthy people and GSD patients in genotype and allele frequencies. However, the genotype for E3/E4 and the APOE4 allele in GSD patients were higher than the controls (9.88% vs. 5.0% and 4.94% vs. 2.5%, respectively; P <0.05) but statistically nonsignificant. serum levels of cholesterol, low-density lipoproteins, and very low-density lipoproteins were higher, and the levels of serum high-density lipoprotein was lower than controls. These findings revealed no connection between the examined polymorphisms and gallstone cases. Additionally, it was demonstrated that gallstone disease and lipid parameters had a favorable relationship. Keywords: Apolipoprotein E, APOE, Gallstone disease, Genotype, Polymorphisms.

Associations between APOE genotypes, urine 8-isoprostane and blood trace elements in middle-aged mothers (CROME study)

BackgroundThere is almost no data on the combined associations between apolipoprotein E gene (APOE) genotypes, trace elements (TEs), and lipid peroxidation in vivo. The aim of our study was to evaluate the association between APOE genotypes and TE levels in blood (B-TEs) and erythrocytes (E-TEs), and 8-isoprostane in urine (U-8-isoprostane) in women with low exposure to potentially toxic TEs and with adequate supply of essential TEs. MethodsB-TEs, E-TEs and U-8-isoprostane were determined in 172 healthy women of childbearing age (30.1–51.4 years) using ICP-MS and ELISA competitive assay, respectively. All women were divided into three APOE genotype groups according to the presence of the ɛ4 allele, ɛ2 allele or ɛ3 homozygotic allele. The associations between B-TEs, E-TE, U-8-isoprostane, and the APOE genotype groups were estimated by multiple variable linear regression models with relevant explanatory variables (e.g., age, BMI, and seafood). ResultsAll TE and U-8-isoprostane levels were inside the reference ranges for the healthy population. In the multiple variable linear regression models, our results showed that urine 8-isoprostane levels increased by up to 43.3% in the APOE4 group compared to the APOE3 group and a negligible negative modifying effect for essential TEs. However, the APOE genotype groups were associated also with some TEs. A clear positive association was found between the APOE2 and APOE4 groups (vs. APOE3) with B-molybdenum. ConclusionsOur study suggests that the APOE4 genotype played an important role in 8-isoprostane variability in a population with an adequate supply of essential and with low exposure to potentially toxic TEs. Adequate copper, zinc and selenium status seemed to be protective against, while the levels of nonessential TEs were probably too low to play a decisive role in 8-isoprostane formation. The observed impact of the APOE2 and APOE4 groups on increased B-molybdenum opens a new research topic.

Application Value of the Apolipoprotein in the Prediction of Acute Ischemic Death and in the Assessment of Functional Outcomes.

In recent years, research on the apolipoprotein E (APOE) gene has gradually proven that many diseases, including atherosclerosis, coronary heart disease, and neurological diseases, are closely related to ApoE gene diversity. However, the relationship between the APOE gene and the prediction and prognosis evaluation of ischemic stroke has not been determined or unified so far. The purpose of this study was to investigate the application value of APOE allele-4 combined with high-resolution vascular wall imaging in predicting the occurrence and prognosis of acute ischemic stroke. A total of 511 patients with acute ischemic stroke (AIS), who were admitted from January 2022 to December 2023, were included in the study, including 317 patients with intracranial artery stenosis. Blood lipids, lipoproteins, apolipoprotein E (including allelic typing), and lipoproteins (a) were measured in all cases, and high-resolution magnetic resonance imaging of the vascular walls was performed. At 6 months, the functional outcomes of the AIS patients were followed up, assessed by using the modified Rankin Scale (mRS) (a score of 2 - 6 was rated as poor prognosis), and the high-definition vascular wall imaging results were followed up as well. High-definition vascular wall imaging ensures the accurate location of vascular stenosis and the accurate diagnosis of acute stroke. There were no significant differences in the total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, or lipoprotein (a) in patients with and without intracranial artery stenosis, but the plasma apolipoprotein E (APOE) levels were significantly reduced in patients with intracranial artery stenosis (ICAS). At the 6-month follow-up, 230 patients with the APOE-ε4 gene were enrolled, out of which 104 had a poor prognosis (mRS score ≥ 2), accounting for 45.22%. Among 281 patients without the APOE-ε4 gene, 45 had a poor prognosis (mRS score ≥ 2), accounting for 16.01%. Patients with the APOE-ε4 gene had a worse functional prognosis after 6 months. It is suggested that low plasma APOE levels may be a high risk factor for ICAS in patients with acute ischemic stroke, and carrying the APOE-ε4 gene may be a high risk factor for a poor functional prognosis in AIS patients. The APOE-ε4 genotype, combined with high-resolution vascular wall imaging, has certain clinical application value in predicting the occurrence of acute ischemic death and evaluating the functional outcome.

APOE gene polymorphism in ischemic stroke patients from Huizhou and its correlation with blood lipids and homocysteine

ObjectivesTo investigate the correlation between apolipoprotein E (APOE) gene polymorphisms and ischemic stroke and its relationship with blood lipids and homocysteine (HCY) level in Huizhou City. Materials and methodsIn this analytical cross-sectional study, we selected 2612 patients who underwent APOE genotyping from November 2019 to November 2021 at the Third People's Hospital of Huizhou. Among them, 2014 were ischemic stroke patients and 598 were non-stroke patients. The independent variables were ischemic stroke, different genotypes, and different alleles, while the dependent variables were blood lipid levels and HCY levels. ResultsThe distribution frequency of ε4 allele in stroke group was higher than that in non-stroke group (P < 0.05). Compared with ε4 allele carriers in the stroke group, the levels of lipid total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in ε2 and ε3 allele carriers were significantly lower, while the levels of high-density lipoprotein cholesterol (HDL-C) were significantly higher (P < 0.01). The levels of lipid Lipoprotein a (LPa) and small dense low-density lipoprotein (sdLDL) in ε2 allele carriers in stroke group were significantly lower than those of ε4 allele carriers (P < 0.05). Logistics regression analysis showed that age, TC, HCY level and allele ε4 were positively correlated with the risk of ischemic stroke (P < 0.01), TG level was positively correlated with the risk of ischemic stroke in females (P < 0.01). ConclusionsAPOE gene polymorphism is associated with ischemic stroke, and ε4 allele carriers have a higher risk than ε3 allele carriers.

Association of polygenic risk scores with Alzheimer's disease and plasma biomarkers among Chinese older adults: A community-based study.

We examined the associations of polygenic risk score (PRS) with Alzheimer's disease (AD) and plasma biomarkers in the Chinese population. This population-based study used baseline data from MIND-China (2018; n=4873) and follow-up data from dementia-free individuals (2014-2018; n=2117). We measured AD-related plasma biomarkers in a subsample (n=1256). Data were analyzed using logistic and Cox regression models. We developed PRS with (PRSAPOE) and without (PRSnon- APOE) apolipoprotein E (APOE) gene. In the longitudinal analysis, PRSAPOE was associated with a multivariable-adjusted hazards ratio of 1.91 (95% CI=1.13-3.23) for AD. PRSAPOE in combination with demographics yielded discriminative (area under the curve [AUC]) and predictive(C-statistic) accuracy of 0.80 (95% confidence interval [CI]=0.77-0.84) and 0.80 (0.77-0.82), respectively. PRSnon- APOE showed an association with AD risk similar to PRSAPOE. PRSAPOE, but not PRSnon- APOE, was associated with reduced plasma Aβ42/Aβ40 ratio and increased Neurofilament light chain (NfL) (p<0.05). The PRS with and without APOE gene, in combination with demographics, shows good discriminative and predictive ability for AD. The AD-related pathologies underlie AD risk associated with PRSAPOE. The PRSAPOE and PRSnon- APOE were associated with AD risk in the Chinese population. The PRSAPOE and PRSnon- APOE, in combination with demographics, showed good discriminative and predictive ability for AD. The AD-related pathologies underlie the AD risk associated with PRSAPOE but not PRSnon- APOE.

Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference.

The apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid-beta and tau pathologies but also lipid and energy metabolism, neuroinflammation, cerebral vascular health, and sex-dependent disease manifestations. Furthermore, ancestral background may significantly impact the link between APOE and AD, underscoring the need for more inclusive research. In 2023, the Alzheimer's Association convened multidisciplinary researchers at the "AAIC Advancements: APOE" conference to discuss various topics, including apoE isoforms and their roles in AD pathogenesis, progress in apoE-targeted therapeutic strategies, updates on disease models and interventions that modulate apoE expression and function. This manuscript presents highlights from the conference and provides an overview of opportunities for further research in the field. Understanding apoE's multifaceted roles in AD pathogenesis will help develop targeted interventions for AD and advance the field of AD precision medicine. APOE is a central player in the pathogenesis of Alzheimer's disease. APOE exerts a numerous effects throughout the brain on amyloid-beta, tau, and other pathways. The AAIC Advancements: APOE conference encouraged discussions and collaborations on understanding the role of APOE.

Apolipoprotein E E3/E4 genotype is associated with an increased risk of premature coronary artery disease

ObjectiveDyslipidemia is one of the causes of coronary heart disease (CAD), and apolipoprotein E (APOE) gene polymorphism affects lipid levels. However, the relationship between APOE gene polymorphisms and premature CAD (PCAD, male CAD patients with ≤ 55 years old and female with ≤ 65 years old) risk had different results in different studies. The aim of this study was to assess this relationship and to further evaluate the relationship between APOE gene polymorphisms and PCAD risk in the Hakka population.MethodsThis study retrospectively analyzed 301 PCAD patients and 402 age matched controls without CAD. The APOE rs429358 and rs7412 polymorphisms were genotyped by polymerase chain reaction (PCR) -chip technique. The distribution of APOE genotypes and alleles between the case group and the control group was compared. The relationship between APOE genotypes and PCAD risk was obtained by logistic regression analysis.ResultsThe frequency of the APOE ɛ3/ɛ4 genotype (18.9% vs. 10.2%, p = 0.001) and ε4 allele (11.1% vs. 7.0%, p = 0.007) was higher in the PCAD patients than that in controls, respectively. PCAD patients with ɛ2 allele had higher TG level than those with ɛ3 allele, and controls carried ɛ2 allele had higher HDL-C level and lower LDL-C level than those carried ɛ3 allele. Regression logistic analysis showed that BMI ≥ 24.0 kg/m2 (BMI ≥ 24.0 kg/m2 vs. BMI 18.5–23.9 kg/m2, OR: 1.763, 95% CI: 1.235–2.516, p = 0.002), history of smoking (Yes vs. No, OR: 5.098, 95% CI: 2.910–8.930, p < 0.001), ɛ3/ɛ4 genotype (ɛ3/ɛ4 vs. ɛ3/ɛ3, OR: 2.203, 95% CI: 1.363–3.559, p = 0.001), ε4 allele (ε4 vs. ε3, OR: 2.125, 95% CI: 1.333–3.389, p = 0.002), and TC level (OR: 1.397, 95% CI: 1.023–1.910, p = 0.036) were associated with PCAD.ConclusionsIn summary, BMI ≥ 24.0 kg/m2, history of smoking, APOE ɛ3/ɛ4 genotype, and TC level were independent risk factors for PCAD. It means that young individuals who are overweight, have a history of smoking, and carried APOE ɛ3/ɛ4 genotype had increased risk of PCAD.

Apolipoprotein E polymorphisms and female fertility in a transgenic mouse model of Alzheimer’s disease

Apolipoprotein E (APOE) is a major cholesterol carrier responsible for lipid transport and injury repair in the brain. The human APOE gene (h-APOE) has 3 naturally occurring alleles: ε3, the common allele; ε4, which increases Alzheimer’s disease (AD) risk up to 15-fold; and ε2, the rare allele which protects against AD. Although APOE4 has negative effects on neurocognition in old age, its persistence in the population suggests a survival advantage. We investigated the relationship between APOE genotypes and fertility in EFAD mice, a transgenic mouse model expressing h-APOE. We show that APOE4 transgenic mice had the highest level of reproductive performance, followed by APOE3 and APOE2. Intriguingly, APOE3 pregnancies had more fetal resorptions and reduced fetal weights relative to APOE4 pregnancies. In conclusion, APOE genotypes impact fertility and pregnancy outcomes in female mice, in concordance with findings in human populations. These mouse models may help elucidate how h-APOE4 promotes reproductive fitness at the cost of AD in later life.

Maternal APOE ε2 as a possible risk factor for elevated prenatal Pb levels

Lead (Pb) is a global contaminant associated with multiple adverse health effects. Humans are especially vulnerable during critical developmental stages. During pregnancy, exposure to Pb can occur through diet and release from maternal bones. Apolipoprotein E gene (APOE) variants (ɛ2, ɛ3, ɛ4 alleles) may influence sex steroid hormones, bone metabolism, and Pb kinetics.We examined the interplay among maternal APOE (mAPOE) genotypes, fetal sex, parity, and Pb in maternal and cord blood (mB-Pb, CB-Pb) using linear regression models. Our study involved 817 pregnant women and 772 newborns with measured adequate levels of zinc and selenium. We compared carriers of the ε2 and ε4 alleles to those with the ε3/ε3 genotype.The geometric means (range) of mB-Pb and CB-Pb were 11.1 (3.58–87.6) and 9.31 (1.82–47.0) ng/g, respectively. In cases with female fetuses, the maternal mAPOE ε2 allele was associated with higher, while the mAPOE ε4 allele was associated with lower mB-Pb and CB-Pb levels. Nulliparity increased the strength of the observed associations. These findings highlight the significance of mAPOE genetics, fetal sex, and parity in prenatal Pb kinetics. Notably, the maternal ε2 allele may increase the risk of Pb exposure.

Multiple Roles of Apolipoprotein E4 in Oxidative Lipid Metabolism and Ferroptosis During the Pathogenesis of Alzheimer’s Disease

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide and has a great socio-economic impact. Modified oxidative lipid metabolism and dysregulated iron homeostasis have been implicated in the pathogenesis of this disorder, but the detailed pathophysiological mechanisms still remain unclear. Apolipoprotein E (APOE) is a lipid-binding protein that occurs in large quantities in human blood plasma, and a polymorphism of the APOE gene locus has been identified as risk factors for AD. The human genome involves three major APOE alleles (APOE2, APOE3, APOE4), which encode for three subtly distinct apolipoprotein E isoforms (APOE2, APOE3, APOE4). The canonic function of these apolipoproteins is lipid transport in blood and brain, but APOE4 allele carriers have a much higher risk for AD. In fact, about 60% of clinically diagnosed AD patients carry at least one APOE4 allele in their genomes. Although the APOE4 protein has been implicated in pathophysiological key processes of AD, such as extracellular beta-amyloid (Aβ) aggregation, mitochondrial dysfunction, neuroinflammation, formation of neurofibrillary tangles, modified oxidative lipid metabolism, and ferroptotic cell death, the underlying molecular mechanisms are still not well understood. As for all mammalian cells, iron plays a crucial role in neuronal functions and dysregulation of iron homeostasis has also been implicated in the pathogenesis of AD. Imbalances in iron homeostasis and impairment of the hydroperoxy lipid-reducing capacity induce cellular dysfunction leading to neuronal ferroptosis. In this review, we summarize the current knowledge on APOE4-related oxidative lipid metabolism and the potential role of ferroptosis in the pathogenesis of AD. Pharmacological interference with these processes might offer innovative strategies for therapeutic interventions.

Single-nucleus transcriptome reveals cell dynamic response of liver during the late chick embryonic development

The late embryonic development of the liver, a major metabolic organ, remains poorly characterized at single cell resolution. Here, we used single-nucleus RNA-sequencing (snRNA-seq) to characterize the chicken liver cells at 2 embryonic development time points (E14 and D1). We uncovered 8 cell types including hepatocytes, endothelial cells, hepatic stellate cells, erythrocytes, cholangiocytes, kupffer cells, mesothelial cells, and lymphocytes. And we discovered significant differences in the abundance of different cell types between E14 and D1. Moreover, we characterized the heterogeneity of hepatocytes, endothelial cells, and mesenchymal cells based on the gene regulatory networks of each clusters. Trajectory analyses revealed 128 genes associated with hepatocyte development and function, including apolipoprotein genes involved hepatic lipid metabolism and NADH dehydrogenase subunits involved hepatic oxidative phosphorylation. Furthermore, we identified the differentially expressed genes (DEGs) between E14 and D1 at the cellular levels, which contribute to changes in liver development and function. These DEGs were significantly enriched in PPAR signaling pathways and lipid metabolism related pathways. Our results presented the single-cell mapping of chick embryonic liver at late stages of development and demonstrated the metabolic changes across the 2 age stages at the cellular level, which can help to further study the molecular development mechanism of embryonic liver.

Ethical concerns in integrating sport-related concussion (SRC) genetic testing into return-to-play (RTP) protocols

ABSTRACT The occurrence of sport-related concussions (SRCs) has emerged as a significant health concern in professional sports, with millions of concussions occurring worldwide each year. Current return-to-play (RTP) protocols after SRCs involve a multi-disciplinary approach with growing interest in genetic testing technology. Numerous studies have indicated that the gene Apolipoprotein E4 (APOE4) holds promise as a predictive factor for developing diseases after concussions and other traumatic brain injuries. Nevertheless, there is an ongoing and contentious debate surrounding the impact of SRC genetic testing on the RTP decision, encompassing concerns about the potential adverse effects on individual athletes, coaches, and even the whole sport community at large not in a small degree due to incidental findings. Hence, the purpose of this article is to explore the clinical and ethical components of SRCs genetic testing and its potential integration into RTP protocols by utilizing the ACCE framework to assess the validity, utility, and ethical aspects of SRCs.

PON1, APOE and SDF-1 Gene Polymorphisms and Risk of Retinal Vein Occlusion: A Case-Control Study.

Numerous studies have tried to evaluate the potential role of thrombophilia-related genes in retinal vein occlusion (RVO); however, there is limited research on genes related to different pathophysiological mechanisms involved in RVO. In view of the strong contribution of oxidative stress and inflammation to the pathogenesis of RVO, the purpose of the present study was to investigate the association of inflammation- and oxidative-stress-related polymorphisms from three different genes [apolipoprotein E (APOE), paraoxonase 1 (PON1) and stromal cell-derived factor 1 (SDF-1)] and the risk of RVO in a Greek population. Participants in this case-control study were 50 RVO patients (RVO group) and 50 healthy volunteers (control group). Blood samples were collected on EDTA tubes and genomic DNA was extracted. Genotyping of rs854560 (L55M) and rs662 (Q192R) for the PON1 gene, rs429358 and rs7412 for the APOE gene and rs1801157 [SDF1-3'G(801)A] for SDF-1 gene was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Multiple genetic models (codominant, dominant, recessive, overdominant and log-additive) and haplotype analyses were performed using the SNPStats web tool to assess the correlation between the genetic polymorphisms and the risk of RVO. Binary logistic regression analysis was used for the association analysis between APOE gene variants and RVO. Given the multifactorial nature of the disease, our statistical analysis was adjusted for the most important systemic risk factors (age, hypertension and diabetes mellitus). The dominant genetic model for the PON1 Q192R single nucleotide polymorphism (SNP) of the association analysis revealed that there was a statistically significant difference between the RVO group and the control group. Specifically, after adjusting for age and hypertension, the PON1 192 R allele (QR + RR) was found to be associated with a statistically significantly higher risk of RVO compared to the QQ genotype (OR = 2.51; 95% CI = 1.02-6.14, p = 0.04). The statistically significant results were maintained after including diabetes in the multivariate model in addition to age and hypertension (OR = 2.83; 95% CI = 1.01-7.97, p = 0.042). No statistically significant association was revealed between the other studied polymorphisms and the risk of RVO. Haplotype analysis for PON1 SNPs, L55M and Q192R, revealed no statistically significant correlation. In conclusion, PON1 192 R allele carriers (QR + RR) were associated with a statistically significantly increased risk of RVO compared to the QQ homozygotes. These findings suggest that the R allele of the PON1 Q192R is likely to play a role as a risk factor for retinal vein occlusion.

Association of Apolipoprotein E (APOE) Polymorphisms With Serological Lipid and Inflammatory Markers.

Background The study aims to assess the association of apolipoprotein E (APOE) gene polymorphisms with serological lipid and inflammatory markers to determine their potential role in predicting the risk of cardiovascular diseases (CVDs) and Alzheimer's disease (AD). Methodology A total of 915 individuals underwent testing for lipid and inflammatory biomarkers at Vibrant America Clinical Laboratory. Clinical data, blood lipid and inflammatory profiles, and APOE genotyping were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results Compared to the E3/E3 genotype, individuals with E2/E3 genotypes showed higher levels of high-density lipoprotein (HDL), triglycerides, apolipoprotein A (APOA), high-sensitivity C-reactive protein (hs-CRP), and myeloperoxidase (MPO). E2/E4 genotype carriers had higher levels of HDL, triglycerides, Lp(a), and N-terminal pro b-type natriuretic peptide (BNPNT). E3/E4 genotypes were associated with elevated levels of total cholesterol, LDL, Lp(a), hs-CRP, small-density low-density lipoprotein (SDLDL), oxidized LDL (OXLDL), MPO, LDL-CAL, PLAC, and APOB. The E4/E4 group displayed higher concentrations of total cholesterol, LDL, APOB, Lp(a), hs-CRP, SDLDL, OXLDL, MPO, LDLCAL, and PLAC compared to E3/E3 carriers. These findings highlight the potential atherogenic effect of the ε4 allele and the protective effect of the ε2 allele based on lipid and inflammatory marker profiles. Conclusions This study provides strong evidence linking APOE gene polymorphism to abnormal serum lipid and inflammatory profiles. Individuals carrying the ε4 alleles exhibited dysregulated lipid metabolism and abnormal inflammatory markers, increasing their risk of CVD and AD. Early detection and prompt diagnosis are crucial for implementing therapeutic, dietary, and lifestyle interventions to mitigate risks and prevent or delay lipid and inflammation-related disorders.

APOE ε4 allele modifies the associations of toxic metals and their mixture with cognitive impairment among older adults

BackgroundThe evidence of interactive effect of the toxic metal (TM) mixture and apolipoprotein E (APOE) ε4 gene on cognitive impairment in older adults is scarce. We aimed to explore whether the associations of single TMs and their mixture with cognitive impairment depend on APOE ε4 in Chinese community-dwelling older people. MethodsA total of 1148 older adults from a subset of the baseline survey of a cohort study were included. Blood arsenic (As), cadmium (Cd), lead (Pb), strontium (Sr), and vanadium (V) were detected by inductively coupled plasma mass spectrometry. APOE gene (rs429358, rs7412) polymorphisms were analyzed by the Polymerase Chain Reaction instrument. Mixed effects logistic regression was applied to estimate the relationships of single TMs and APOE genotype with cognitive impairment. Weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were performed to examine joint impacts of the TM mixture, as well as the interaction of the TM mixture with APOE ε4 genotype on cognitive impairment. ResultsPb displayed a significant linear association with an increased odds of cognitive impairment after adjustment for covariates (Ptrend = 0.045). While APOE genotype did not show a significant correlation with cognitive impairment. WQS showed that the TM mixture was associated with an increased risk of cognitive impairment by 31.0% (OR=1.31, 95% CI: 0.92, 1.87) while no significance was found. BKMR exhibited a significant linear association between the TM mixture and cognitive impairment. Moreover, both WQS and BKMR indicated that Pb contributed the most to cognitive impairment within the mixture. Significant interactions of Pb or the TM mixture and APOE genotype on cognitive impairment were observed, contributing to 38.1% and 38.2% of total effects, respectively. ConclusionsAPOE ε4 allele amplifies the associations of single Pb or the TM mixture with cognitive impairment. These findings may help to develop precision prevention.

Sex differences in a novel transgenic mouse model of Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common form of dementia characterized by memory deficits, cognitive impairment, and presence of amyloid plaques and tau tangles in the brain. In the United States, six million people over the age of 65 live with AD, four million of whom are women. The apolipoprotein ( APOE) gene is the strongest genetic risk factor for late-onset AD, with the ε4 allele increasing AD risk relative to the ε3 allele. Mechanisms driving sex-based prevalence in the APOE4 genotype remain unknown. Previously, we have reported that female APOE4 mice develop hypertension and increased levels of vasoconstrictor angiotensin II (Ang II) in CSF with aging [FASEB J 2022: 36S1]. To better recapitulate human AD pathology and phenotype, we have recently generated unique mouse strains - 3XE4 and 3XE3 mice, by breeding human APOE4/APOE3-knockin with APPsw, PS1dE9, and tauP301S transgenes. Our goal is to study sex differences in the 3XE4 mice with AD. Blood pressure (BP, tail cuff), cognition (novel object recognition test), and cardiac function (echocardiography) were measured in both control 3XE3 (n=6) mice and 3XE4 (n=6) mice before and after Ang II (osmotic minipump, 1000 ng/kg/min). As expected, female mice weighed less than the male mice (Table). Basal BP and ejection fraction were higher in male 3XE4 mice compared to female 3XE4 mice (p&lt;0.05). Total exploration time of novel object was significantly delayed in 3XE4 mice (p&lt;0.05); the impairment was greater in the female 3XE4 mice. Notably, Ang II increased BP in male 3XE4 mice (151±5 mmHg) but not in female 3XE4 mice (125±2 mmHg). Unlike the 3XE3 mice, total exploration time of novel object was delayed (impaired) in both male and female 3XE4 mice at baseline and during Ang II. Although additional studies are needed to explore the underlying mechanisms, our results implicate potential sexual dimorphism in blood pressure regulation and cognition in Alzheimer’s Disease. [Formula: see text] Funding: NIH R01HL149677 and R21AG070188. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Relationship of Hearing Loss to Parkinson's Disease, Dementia, and APOE Genotype in Adults.

Background: Hearing loss has been recognized as a risk factor for dementia and non-motor features of Parkinson's disease (PD). The apolipoprotein E (APOE) protein contributes to maintenance and repair of neuronal cell membranes, causing age-related disorders. This study aimed to analyze the impact of hearing loss on cognitive impairment, PD severity, and APOE gene expression in these patients. Methods: A total of 72 out-patients diagnosed with either PD or hearing loss were enrolled in this study. The hearing assessment included pure-tone audiometry, speech reception thresholds, and speech discrimination ability. Dementia was assessed by filling out the Clinical Dementia Rating and Mini-Mental State Examination questionnaires. The severity of PD was assessed using the Modified Hoehn and Yahr scale. Blood samples were tested for the gene expression of APOE. Results: Out of the 72 cases, there were 44 males and 28 females, with an average age of 64.4 ± 9.1 years. A total of 41 out of 72 cases had dementia and had a worse hearing threshold than those without dementia (47.1 ± 24.4 vs. 31.7 ± 22.1 dB, p = 0.006). A total of 58 patients were diagnosed with PD, with 14 of them classified as having severe symptoms (Modified Hoehn and Yahr scale > 2). Patients with severe PD were found to have a worse hearing threshold (49.6 ± 28.3 vs. 30.3 ± 17.8 dB, p = 0.028) and higher prevalence of dementia (12/14 vs. 18/44, p = 0.006). Among 10 individuals with the APOE ε4 gene, the prevalence of dementia was higher than those without the ε4 allele (9/10 vs. 32/62, p = 0.036). Conclusions: Hearing loss is common in severe PD and in dementia patients. Severe PD has a negative impact on the hearing threshold and cognitive dysfunction. Patients with APOE ε4 have a higher prevalence of dementia.