A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation.

BACKGROUND: This article reports an extremely rare case of lipoprotein glomerulopathy (LPG) with apolipoprotein E gene (APOE) Chicago mutation in a young Chinese male. Only five cases or families with APOE Chicago mutations have been reported in the literature. CASE PRESENTATION: The young male patient is manifested with nephrotic syndrome, accompanied by hyperlipidemia with a preferable increase in triglycerides and elevated ApoE level. Renal biopsy of the patient showed highly dilated glomerular capillaries filled with vacuolar lipids, segmentally fused podocyte foot processes, vacuolar degeneration of renal tubular epithelial cells and absence of electron-dense material, which indicates the diagnosis of LPG. Whole-exome gene sequencing identified the heterozygous mutation of NM_000041.4:c.494G > C (p.Arg165Pro), which is in the exon 4 of the APOE gene and also known as APOE Chicago mutation, a rare mutation of LPG. Further family pedigree gene analysis clarified that the mutation was inherited from the patient's mother, who does not have high ApoE levels or renal manifestations. This is also consistent with the incomplete penetrance of APOE gene mutations in LPG. Under lipid-lowering treatments, including a low-fat diet and fenofibrate, the patient's urinary protein was partially controlled, and the albumin level was recovered. CONCLUSION: Patients with nephrotic syndrome and elevated ApoE levels should be prompted into renal biopsy to avoid delay of appropriate treatment and unnecessary use of glucocorticoids. This case of LPG was diagnosed by renal biopsy and further verified with genetic sequencing. The timely diagnosis and treatment improved the patient's symptoms. This case is one of only six reported LPG cases or families with APOE Chicago mutation in the world.

Protective Association of APOC1/rs4420638 with Risk of Obesity: A case-control Study in Portuguese Children.

The association of the rs4420638 polymorphism, near the APOC1 gene, was examined with the risk of obesity among Portuguese children. A sample of 446 Portuguese individuals (231 boys and 215 girls) of European descent, aged 3.2 to 13.7 years old (mean age: 7.98 years), were selected to conduct a case-control study. Body mass index (BMI), BMI Z-scores, and waist circumference were calculated. Genotyping was performed by real time PCR using a pre-designed TaqMan probe. Logistic regression and the nonparametric Mann-Whitney test were used to test the associations. The association results revealed a significant protective effect from the minor G-allele of SNP rs4420638 against obesity, with an odds ratio (OR) of 0.619 (95% CI 0.421-0.913; p = 0.0155) in the additive model, and OR of 0.587 (95% CI 0.383-0.9; p = 0.0145) in the dominant model. Moreover, comparing genotype groups (AA vs. AG + GG), significantly lower values (p < 0.05) for the anthropometric traits weight, height, BMI, BMI Z-score and waist circumference, were observed in the carriers of allele G. The present study provides further evidence for the APOE/APOC1 candidate-region association with the risk of obesity. This was the first study to describe the protective association of the rs4420638 minor G-allele against obesity in childhood exclusively.

Correlation analysis of peripheral platelet markers and disease phenotypes in Alzheimer's disease.

INTRODUCTION: Platelets serve as the primary peripheral reservoir of amyloid beta (Aß). However, there is limited research on platelet markers in routine blood examinations, particularly with regard to the large platelet ratio (P-LCR) in Alzheimer's disease (AD). METHODS: This study included 512 AD patients and 205 healthy controls (HCs). Platelet markers and apolipoprotein E (APOE) 4 status were assessed in all participants. RESULTS: The study revealed that P-LCR was significantly elevated in AD patients compared to HCs. In AD patients carrying APOE4, P-LCR significantly negatively correlated with Montreal Cognitive Assessment scores. There was an observed increasing trend in the rate of change in P-LCR with disease progression. Binary logistic regression analysis indicated that P-LCR may constitute a risk factor for AD, after adjusting for age, sex, APOE4, and body mass index. DISCUSSION: P-LCR is associated with disease severity in AD patients carrying APOE4. P-LCR may be a promising marker to reflect platelet activity in AD patients. HIGHLIGHTS: P-LCR significantly negatively correlated with MoCA scores in AD patients with APOE4. The rate of change in P-LCR showed an increasing trend with disease progression. P-LCR may be a risk factor for AD.

Resting-state brain signal complexity discriminates young healthy APOE e4 carriers from non-e4 carriers.

It is well established that the e4 allele of the APOE gene is associated with impaired brain functionality and cognitive decline in humans at elder age. However, it is controversial whether and how the APOE e4 allele is associated with superior brain function among young healthy individuals, thus indicates a case of antagonistic pleiotropy of APOE e4 allele. Signal complexity is a critical aspect of brain activity that has been associated with brain function. In this study, the multiscale entropy (MSE) of resting-state EEG signals among a sample of young healthy adults (N = 260) as an indicator of brain signal complexity was investigated. It was of interest whether MSE differs across APOE genotype groups while age and education level were controlled for and whether the APOE genotype effect on MSE interacts with MSE time scale, as well as EEG recording condition. Results of linear mixed models indicate overall larger MSE in APOE e4 carriers. This genotype-dependent difference is larger at high as compared with low time scales. The interaction effect between APOE genotype and recording condition indicates increased between-state MSE change in young healthy APOE e4 carriers as compared with non-carriers. Because higher complexity is commonly taken to be associated with better cognitive functioning, the present results complement previous findings and therefore point to a pleiotropic spectrum of the APOE gene polymorphism.

Validation of newly derived polygenic risk scores for dementia in a prospective study of older individuals.

INTRODUCTION: Recent genome-wide association studies identified new dementia-associated variants. We assessed the performance of updated polygenic risk scores (PRSs) using these variants in an independent cohort. METHODS: We used Cox models and area under the curve (AUC) to validate new PRSs (PRS-83SNP, PRS-SBayesR, and PRS-CS) compared with an older PRS-23SNP in 12,031 initially-healthy participants ≥70 years of age. Dementia was rigorously adjudicated according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. RESULTS: PRS-83SNP, PRS-SBayesR, and PRS-CS were associated with incident dementia, with fully adjusted (including apolipoprotein E [APOE] ε4) hazard ratios per standard deviation (SD) of 1.35 (1.23-1.47), 1.37 (1.25-1.50), and 1.42 (1.30-1.56), respectively. The AUC of a model containing conventional/non-genetic factors and APOE was 74.7%. This was improved to 75.7% (p = 0.007), 76% (p = 0.004), and 76.1% (p = 0.003) with addition of PRS-83SNP, PRS-SBayesR, and PRS-CS, respectively. The PRS-23SNP did not improve AUC (74.7%, p = 0.95). CONCLUSION: New PRSs for dementia significantly improve risk-prediction performance, but still account for less risk than APOE genotype overall.

Alzheimer's Disease: Causal Effect between Obesity and APOE Gene Polymorphisms.

Currently studies on the correlation between obesity and Alzheimer's disease (AD) are still unclear. In addition, few indicators have been used to evaluate obesity, which has failed to comprehen-sively study the correlations between body fat mass, body fat distribution, and AD. Thus, this study innovatively utilized bioinformatics and Mendelian randomization (MR) to explore the key targets of obesity-induced AD, and investigate the causal associations between different types of obesity and key targets. The common targets of obesity and AD were screened using the GeneCards database, and functional and pathway annotations were carried out, thereby revealing the key target. MR analysis was conducted between body anthropometric indexes of obesity and the key target using an IVW model. Bioinformatics analysis revealed Apolipoprotein E (APOE) as the key target of obesity-induced AD. MR results showed that body mass index (BMI) had a negative causal association with APOE2, while body fat percentage (BFP) and trunk fat percentage (TFP) had no significant causal association with APOE2; BMI, BFP, and TFP had a negative causal association with APOE3, and none had any significant causal association with APOE4. In conclusion, there is a correlation between obesity and AD, which is mainly due to the polymorphism of the APOE gene rather than adipose tissue distribution. APOE3 carriers may be more susceptible to obesity, while the risk of AD caused by APOE2 and APOE4 may not be induced by obesity. This study sheds new light on current disputes. At the same time, it is suggested to regulate the body fat mass of APOE3 carriers in the early stage, and to reduce the risk of AD.

Establishing the relationship between familial dysbetalipoproteinemia and genetic variants in the APOE gene.

Familial Dysbetalipoproteinemia (FD) is the second most common monogenic dyslipidemia and is associated with a very high cardiovascular risk due to cholesterol-enriched remnant lipoproteins. FD is usually caused by a recessively inherited variant in the APOE gene (ε2ε2), but variants with dominant inheritance have also been described. The typical dysbetalipoproteinemia phenotype has a delayed onset and requires a metabolic hit. Therefore, the diagnosis of FD should be made by demonstrating both the genotype and dysbetalipoproteinemia phenotype. Next Generation Sequencing is becoming more widely available and can reveal variants in the APOE gene for which the relation with FD is unknown or uncertain. In this article, two approaches are presented to ascertain the relationship of a new variant in the APOE gene with FD. The comprehensive approach consists of determining the pathogenicity of the variant and its causal relationship with FD by confirming a dysbetalipoproteinemia phenotype, and performing in vitro functional tests and, optionally, in vivo postprandial clearance studies. When this is not feasible, a second, pragmatic approach within reach of clinical practice can be followed for individual patients to make decisions on treatment, follow-up, and family counseling.

APOE ε4 and late-life cognition: mediation by structural brain imaging markers.

The apolipoprotein E allele 4 (APOE-ε4) is established as a major genetic risk factor for cognitive decline and late-onset Alzheimer's disease. Accumulating evidence has linked ε4 carriership to abnormal structural brain changes across the adult lifespan. To better understand the underlying causal mechanisms, we investigated the extent to which the effect of the ε4 allele on cognition is mediated by structural brain imaging markers in the population-based Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik). This study included 4527 participants (aged 76.3 ± 5.4 at baseline) who underwent the brain magnetic resonance imaging assessment (of brain tissue volumes, white matter lesion volume, subcortical and cortical infarcts, and cerebral microbleeds) and a battery of neuropsychological tests at baseline. Causal mediation analysis was used to quantify the mediation of the ε4 effect on cognition by these MRI markers, both individually and jointly. We observed that about 9% of the total effect of ε4 carriership on cognition was mediated by white matter lesion volume. This proportion increased to 25% when total brain tissue volume was jointly considered with white matter lesion volume. In analyses separating ε4 homozygotes from ε4 heterozygotes, the effect on global cognition of specifically ε4 homozygosity appeared to be partially mediated by cerebral microbleeds, particularly lobar microbleeds. There was no evidence of mediation of the ε4 effect by cortical or subcortical infarcts. This study shows that the ε4 effect on cognition is partly mediated by white matter lesion volume and total brain tissue volume. These findings suggest the joint role of cerebral small vessel disease and neurodegeneration in the ε4-cognition relationship.

APOE Molecular Spectrum in a French Cohort with Primary Dyslipidemia.

Primary hypercholesterolemia is characterized by elevated LDL-cholesterol (LDL-C) levels isolated in autosomal dominant hypercholesterolemia (ADH) or associated with elevated triglyceride levels in familial combined hyperlipidemia (FCHL). Rare APOE variants are known in ADH and FCHL. We explored the APOE molecular spectrum in a French ADH/FCHL cohort of 5743 unrelated probands. The sequencing of LDLR, PCSK9, APOB, and APOE revealed 76 carriers of a rare APOE variant, with no mutation in LDLR, PCSK9, or APOB. Among the 31 APOE variants identified here, 15 are described in ADH, 10 in FCHL, and 6 in both probands. Five were previously reported with dyslipidemia and 26 are novel, including 12 missense, 5 synonymous, 2 intronic, and 7 variants in regulatory regions. Sixteen variants were predicted as pathogenic or likely pathogenic, and their carriers had significantly lower polygenic risk scores (wPRS) than carriers of predicted benign variants. We observed no correlation between LDL-C levels and wPRS, suggesting a major effect of APOE variants. Carriers of p.Leu167del were associated with a severe phenotype. The analysis of 11 probands suggests that carriers of an APOE variant respond better to statins than carriers of a LDLR mutation. Altogether, we show that the APOE variants account for a significant contribution to ADH and FCHL.

Residence, Clinical Features, and Genetic Risk Factors Associated with Symptoms of COVID-19 in a Cohort of Older People in Madrid.

BACKGROUND: The older population has been especially affected by the severe acute respiratory syndrome coronavirus 2 pandemic (COVID-19). OBJECTIVE: The aim of the study was to explore the incidence, severity, mortality rate, clinical features, and risk factors of symptoms of COVID-19 in home-dwelling older people, and its association with type of residence, cognitive deterioration, and neurodegenerative diseases. METHODS: Data about symptoms of COVID-19 were collected through a telephone survey in the cohort of 913 older volunteers of the Vallecas Project, aged 75-90 years, most of them (902) home-dwelling, in Madrid, Spain. The association of demographic and anthropometric measures, genetic polymorphisms, comorbidities, life habits, type of residence, and frailty surrogates were explored as potential risk factors for the incidence, severity, and mortality of COVID-19 in the older population. FINDINGS: Sixty-two cases reported symptoms compatible with COVID-19; 6 of them had died, 4 in their home and 2 in the nursing home. Moderate/severe cases were significantly older and more frequently males. The APOE ε4 allele was associated with the presence of symptoms of COVID-19. Higher systolic blood pressure, more intense smoking habit, more alcohol intake, lower consumption of coffee and tea, and cognitive impairment were associated with disease severity. CONCLUSIONS: The estimated incidence of symptomatic COVID-19 in this older cohort of Madrid was 6.8%, with an overall mortality rate of 0.7% (18.2% in those living in a nursing home) and a fatality rate of 9.9%. Our exploratory study indicates that life habits, other clinical conditions and, the ε4 variant of the APOE gene are associated with the presence and clinical severity of coronavirus infection.

Possible synergistic effect of apoE and LRP1 genotypes on metabolic syndrome development in Serbian patients.

The modern way of life contributes to the higher frequency of a complex state medically called metabolic syndrome (MetS), which is an inevitable consequence of several most common diseases of modern civilization. Patients with MetS have three times higher risk of experiencing a heart attack or a stroke and twice higher possibility to die from them. Serbia holds the infamous third place in Europe in mortality from heart disease, just behind Russia and Ukraine. The study explores the correlation of every combination of genotypes of apoE (apolipoprotein E) and LRP1 (low density receptor- related protein 1) genes with presence of MetS, and the connection with each anthropometric and biochemical parameter in both tested groups. Study demonstrates the impact of genotype combinations on the emergence and development of the MetS in Serbia. 63 patients and 30 controls were included in the study, aged from 19 to 65. Each person genotype was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) profile. Odds ratio (OR) values showed that the presence of apoE e3e4/LRP1 CC genotype combination of genotypes in patients multiplies the chance (7.6 times) for the occurrence of the MetS in comparison to the presence of other genotype combinations. Determining the genetic basis of MetS is one of the necessary steps in the prevention of disease, saving the cost of treatment, and in the design of targeted therapies.

Differential Methylation in APOE (Chr19; Exon Four; from 44,909,188 to 44,909,373/hg38) and Increased Apolipoprotein E Plasma Levels in Subjects with Mild Cognitive Impairment.

BACKGROUND: Biomarkers are essential for identification of individuals at high risk of mild cognitive impairment (MCI) for potential prevention of dementia. We investigated DNA methylation in the APOE gene and apolipoprotein E (ApoE) plasma levels as MCI biomarkers in Colombian subjects with MCI and controls. METHODS: In total, 100 participants were included (71% women; average age, 70 years; range, 43⁻91 years). MCI was diagnosed by neuropsychological testing, medical and social history, activities of daily living, cognitive symptoms and neuroimaging. Using multivariate logistic regression models adjusted by age and gender, we examined the risk association of MCI with plasma ApoE and APOE methylation. RESULTS: MCI was diagnosed in 41 subjects (average age, 66.5 ± 9.6 years) and compared with 59 controls. Elevated plasma ApoE and APOE methylation of CpGs 165, 190, and 198 were risk factors for MCI (p < 0.05). Higher CpG-227 methylation correlated with lower risk for MCI (p = 0.002). Only CpG-227 was significantly correlated with plasma ApoE levels (correlation coefficient = -0.665; p = 0.008). CONCLUSION: Differential APOE methylation and increased plasma ApoE levels were correlated with MCI. These epigenetic patterns require confirmation in larger samples but could potentially be used as biomarkers to identify early stages of MCI.

Association of apolipoprotein E gene polymorphisms with blood lipids and their interaction with dietary factors.

BACKGROUND: Several candidate genes have been identified in relation to lipid metabolism, and among these, lipoprotein lipase (LPL) and apolipoprotein E (APOE) gene polymorphisms are major sources of genetically determined variation in lipid concentrations. This study investigated the association of two single nucleotide polymorphisms (SNPs) at LPL, seven tagging SNPs at the APOE gene, and a common APOE haplotype (two SNPs) with blood lipids, and examined the interaction of these SNPs with dietary factors. METHODS: The population studied for this investigation included 660 individuals from the Prevention of Cancer by Intervention with Selenium (PRECISE) study who supplied baseline data. The findings of the PRECISE study were further replicated using 1238 individuals from the Caerphilly Prospective cohort (CaPS). Dietary intake was assessed using a validated food-frequency questionnaire (FFQ) in PRECISE and a validated semi-quantitative FFQ in the CaPS. Interaction analyses were performed by including the interaction term in the linear regression model adjusted for age, body mass index, sex and country. RESULTS: There was no association between dietary factors and blood lipids after Bonferroni correction and adjustment for confounding factors in either cohort. In the PRECISE study, after correction for multiple testing, there was a statistically significant association of the APOE haplotype (rs7412 and rs429358; E2, E3, and E4) and APOE tagSNP rs445925 with total cholesterol (P = 4 × 10- 4 and P = 0.003, respectively). Carriers of the E2 allele had lower total cholesterol concentration (5.54 ± 0.97 mmol/L) than those with the E3 (5.98 ± 1.05 mmol/L) (P = 0.001) and E4 (6.09 ± 1.06 mmol/L) (P = 2 × 10- 4) alleles. The association of APOE haplotype (E2, E3, and E4) and APOE SNP rs445925 with total cholesterol (P = 2 × 10- 6 and P = 3 × 10- 4, respectively) was further replicated in the CaPS. Additionally, significant association was found between APOE haplotype and APOE SNP rs445925 with low density lipoprotein cholesterol in CaPS (P = 4 × 10- 4 and P = 0.001, respectively). After Bonferroni correction, none of the cohorts showed a statistically significant SNP-diet interaction on lipid outcomes. CONCLUSION: In summary, our findings from the two cohorts confirm that genetic variations at the APOE locus influence plasma total cholesterol concentrations, however, the gene-diet interactions on lipids require further investigation in larger cohorts.

Effect of age and the APOE gene on metabolite concentrations in the posterior cingulate cortex.

Proton magnetic resonance spectroscopy (1H-MRS) has provided valuable information about the neurochemical profile of Alzheimer's disease (AD). However, its clinical utility has been limited in part by the lack of consistent information on how metabolite concentrations vary in the normal aging brain and in carriers of apolipoprotein E (APOE) ε4, an established risk gene for AD. We quantified metabolites within an 8cm3 voxel within the posterior cingulate cortex (PCC)/precuneus in 30 younger (20-40 years) and 151 cognitively healthy older individuals (60-85 years). All 1H-MRS scans were performed at 3T using the short-echo SPECIAL sequence and analyzed with LCModel. The effect of APOE was assessed in a sub-set of 130 volunteers. Older participants had significantly higher myo-inositol and creatine, and significantly lower glutathione and glutamate than younger participants. There was no significant effect of APOE or an interaction between APOE and age on the metabolite profile. Our data suggest that creatine, a commonly used reference metabolite in 1H-MRS studies, does not remain stable across adulthood within this region and therefore may not be a suitable reference in studies involving a broad age-range. Increases in creatine and myo-inositol may reflect age-related glial proliferation; decreases in glutamate and glutathione suggest a decline in synaptic and antioxidant efficiency. Our findings inform longitudinal clinical studies by characterizing age-related metabolite changes in a non-clinical sample.

Apolipoprotein E (APOE) ϵ4 Allele Is Associated with Increased Symptom Reporting Following Sports Concussion.

Exploring the relationship between genetic factors and outcome following brain injury has received increased attention in recent years. However, few studies have evaluated the influence of genes on specific sequelae of concussion. The purpose of this study was to determine how the ϵ4 allele of the apolipoprotein E (APOE) gene influences symptom expression following sports-related concussion. Participants included 42 collegiate athletes who underwent neuropsychological testing, including completion of the Post-Concussion Symptom Scale (PCSS), within 3 months after sustaining a concussion (73.8% were evaluated within 1 week). Athletes provided buccal samples that were analyzed to determine the make-up of their APOE genotype. Dependent variables included a total symptom score and four symptom clusters derived from the PCSS. Mann-Whitney U tests showed higher scores reported by athletes with the ϵ4 allele compared to those without it on the total symptom score and the physical and cognitive symptom clusters. Furthermore, logistic regression showed that the ϵ4 allele independently predicted those athletes who reported physical and cognitive symptoms following concussion. These findings illustrate that ϵ4+ athletes report greater symptomatology post-concussion than ϵ4- athletes, suggesting that the ϵ4 genotype may confer risk for poorer post-concussion outcome. (JINS, 2016, 22, 89-94).

Association of apolipoprotein E polymorphism with plasma lipid disorders, independent of obesity-related traits in Vietnamese children.

BACKGROUND: The dyslipidemia associated with obesity plays a major role in the development of atherosclerosis and cardiovascular disease. Dyslipidemia in childhood can progress in adult stage. APOE is one of the most important genes that regulate plasma lipid transport and clearance. The study aimed to assess whether the common APOE polymorphism is associated with lipid profiles and dyslipidemia, and it could be modulated by obesity-related traits (body mass index, waist circumference, hip circumference, and waist-to-hip ratio) in Vietnamese children. METHODS: A case-control study was designed including 249 cases with dyslipidemia and 600 controls without dyslipidemia. Dyslipidemia is defined as elevated total or low-density lipoprotein (LDL) cholesterol levels, or low levels of high-density lipoprotein (HDL) cholesterol. Genotype for APOE polymorphism (rs7412 and rs429358) was determined by the polymerase chain reaction and restriction fragment length polymorphism method. The association of APOE genotypes with plasma lipid disorders was tested by binary logistic regression analysis, taking into account the confounding factors of age, sex, residence, province and obesity-related traits. RESULTS: In comparison with ε3/ε3 carriers, the ε4 carriers had the highest concentration of serum TC and LDL-C in cases and controls (P ≤ 0.001), while ε2 carriers had the lowest. Carriers without TT haplotype had higher serum TC than those with TT haplotype. The ε4 carriers had higher hypoalphalipoproteinemia risk than ε3/ε3 carriers (OR = 2.78, P = 0.02) before and after adjustment for age, gender, residence and obesity-related traits. CONCLUSIONS: The study suggested that the APOE genotype and haplotype significantly associated with plasma TC and LDL-C level in Vietnamese children. The association of APOE genotype with hypoalphalipoproteinemia was independent of obesity-related traits.

Reduced cerebrovascular reactivity in young adults carrying the APOE ε4 allele.

BACKGROUND: Functional magnetic resonance imaging (MRI) studies have shown that APOE ε2- and ε4-carriers have similar patterns of blood-oxygenation-level-dependent (BOLD) activation suggesting that we need to look beyond the BOLD signal to link APOE's effect on the brain to Alzheimer's disease (AD)-risk. METHODS: We evaluated APOE-related differences in BOLD activation in response to a memory task, cerebrovascular reactivity using a CO2-inhalation challenge (CO2-CVR), and the potential contribution of CO2-CVR to the BOLD signal. RESULTS: APOE ε4-carriers had the highest task-related hippocampal BOLD signal relative to non-carriers. The largest differences in CO2-CVR were between ε2- and ε4-carriers, with the latter having the lowest values. Genotype differences in CO2-CVR accounted for ∼70% of hippocampal BOLD differences between groups. CONCLUSION: Because CO2-CVR gauges vascular health, the differential effect of APOE in young adults may reflect a vascular contribution to the vulnerability of ε4-carriers to late-life pathology. Studies confirming our findings are warranted.

Gene-behavior interaction of depressive symptoms and the apolipoprotein E {varepsilon}4 allele on cognitive decline.

OBJECTIVE: Depressive symptoms and the apolipoprotein E (APOE) ε4 allele are independent risk factors for cognitive decline. However, it is not clear whether the presence of both depressive symptoms and the APOE ε4 allele increases cognitive decline. METHODS: A prospective study of a population-based sample of 4150 (70% African American and 63% women) participants 65 years and older who were interviewed at 3-year intervals was conducted. Depressive symptoms were measured using the 10-item version of the Center for Epidemiologic Studies Depression scale, with each item coded as presence or absence of a symptom. The APOE genotype was ascertained by DNA samples collected during follow-up. Cognitive function was assessed at the initial and follow-up interviews (average follow-up of 9.2 years), using a standardized global cognitive score. RESULTS: There were 1405 (34%) participants with one or more copies of the APOE ε4 allele. In participants with no depressive symptoms, cognitive function decreased by 0.0412 unit per year among those with no copies and 0.0704 unit per year among those with one or more copies of the APOE ε4 allele. For each additional symptom of depression, cognitive decline increased by 0.0021 unit per year among those with no copies and 0.0051 unit per year among those with one or more copies of the APOE ε4 allele. The three-way interaction of depressive symptoms, APOE ε4 allele, and time was significant (p = .021). CONCLUSIONS: The association of depressive symptoms on cognitive decline was increased among participants with one or more copies of the APOE ε4 allele compared with those without the allele.

APOE Gene Variation's Impact on Cardiovascular Health: A Case-Control Study.

Chronic venous insufficiency (CVI) is a common medical condition characterized by impaired functioning of the venous system in the lower extremities. It leads to various symptoms, including varicose veins, leg edema, and skin pigmentation. It is believed that a combination of genetic and environmental factors affect the development of CVI. The APOE gene is of particular interest in this context, as it plays a role in lipid metabolism and inflammation. The ε4 allele (rs429358) has been associated with an increased risk of Alzheimer's disease, while the ε2 allele (rs7412) has shown a protective effect against Alzheimer's disease but a strong association with cardiovascular inflammation. This research aimed to investigate the presence of APOE gene variants in individuals with chronic venous insufficiency disease and validate the relationship between this gene and cardiovascular diseases. The study analyzed the expression of APOE gene variants in varicose vein tissue samples from patients and a normal vein in the control group. The results indicated no significant expression of the ε4 allele in either group. However, there was a significant decrease in the expression of the ε2 allele in the patient group. Additionally, a negative correlation was observed between the two single nucleotide polymorphisms (SNPs) in vein tissue. The lower expression of the ε2 allele in patients suggests a potentially reduced risk of cardiovascular disease in these individuals. Consequently, there appears to be a weaker association between the expression of the APOE gene ε2 allele and cardiovascular diseases.