Influence Of Apolipoprotein Research Articles

Influence of apolipoprotein E gene polymorphisms on coronary artery disease in patients undergoing coronary angiography

ObjectivePrevious studies have shown that apolipoprotein E (ApoE) gene polymorphisms have an impact on coronary artery disease(CAD). However, many studies have small sample sizes and different conclusions. The purpose was to retrospectively study the influence of ApoE gene polymorphisms on CAD. MethodsThis study assessed the influence of different ApoE genotypes on coronary heart disease in patients who received coronary angiography and used multivariate logistic regression to assess the influence of different ApoE genotypes on CAD. ResultsPatients with different ApoE genotypes had no obvious differences in the incidence of hypertension, diabetes or obesity（P > 0.05). Patients with ε2/ε2 had higher incidence of hypertriglyceridemia than patients with other ApoE genotypes, while patients with ε3/ε3 had a lower incidence of hypertriglyceridemia than those with ε3/ε4,ε4/ε4, ε2/ε3 and ε2/ε2（P < 0.05）. Patients with ε3/ε4, ε4/ε4, ε3/ε3 and ε2/ε2 had no significant differences in the severity or incidence of CAD （P > 0.05). ε2/ε4 and ε2/ε3 reduced the risk of high LDL-C, and reduced the severity and incidence of coronary heart（P < 0.05). ε2/ε3 reduced risk of premature coronary artery disease（PCAD）（P < 0.05). ε2/ε3 reduced risk of CAD in patients age <45,age at 60–74 and age ≥74, while ε2/ε4 reduced risk of CAD in patients age ≥74（P < 0.05). ConclusionPatients with ε3/ε4, ε4/ε4,ε3/ε3 and ε2/ε2 had no significant differences in the severity and occurrence of CAD. Compared to the isoform ε3 (ε3/ε3), isoform ε4 did not increased the severity and occurrence of CAD. Compared with ApoE other genotypes, ε2/ε3 and ε2/ε4 reduced the risk of high LDL-C and the severity and occurrence of CAD.

Impact of apolipoprotein E isoforms on sporadic Alzheimer's disease: beyond the role of amyloid beta.

The impact of apolipoprotein E (ApoE) isoforms on sporadic Alzheimer's disease has long been studied; however, the influences of apolipoprotein E gene (APOE) on healthy and pathological human brains are not fully understood. ApoE exists as three common isoforms (ApoE2, ApoE3, and ApoE4), which differ in two amino acid residues. Traditionally, ApoE binds cholesterol and phospholipids and ApoE isoforms display different affinities for their receptors, lipids transport and distribution in the brain and periphery. The role of ApoE in the human depends on ApoE isoforms, brain regions, aging, and neural injury. APOE ε4 is the strongest genetic risk factor for sporadic Alzheimer's disease, considering its role in influencing amyloid-beta metabolism. The exact mechanisms by which APOE gene variants may increase or decrease Alzheimer's disease risk are not fully understood, but APOE was also known to affect directly and indirectly tau-mediated neurodegeneration, lipids metabolism, neurovascular unit, and microglial function. Consistent with the biological function of ApoE, ApoE4 isoform significantly altered signaling pathways associated with cholesterol homeostasis, transport, and myelination. Also, the rare protective APOE variants confirm that ApoE plays an important role in Alzheimer's disease pathogenesis. The objectives of the present mini-review were to describe classical and new roles of various ApoE isoforms in Alzheimer's disease pathophysiology beyond the deposition of amyloid-beta and to establish a functional link between APOE, brain function, and memory, from a molecular to a clinical level. APOE genotype also exerted a heterogeneous effect on clinical Alzheimer's disease phenotype and its outcomes. Not only in learning and memory but also in neuropsychiatric symptoms that occur in a premorbid condition. Clarifying the relationships between Alzheimer's disease-related pathology with neuropsychiatric symptoms, particularly suicidal ideation in Alzheimer's disease patients, may be useful for elucidating also the underlying pathophysiological process and its prognosis. Also, the effects of anti-amyloid-beta drugs, recently approved for the treatment of Alzheimer's disease, could be influenced by the APOE genotype.

Influence of apolipoprotein E (apoE) on ADAM10 secretase in cerebrospinal fluid of older adults with Alzheimer’s disease

AbstractBackgroundThe ε4 allele of APOE is the strongest genetic risk for sporadic late‐onset Alzheimer’s disease (AD), and is associated with an increase in the levels of β‐amyloid (Aβ) deposition. The main α‐secretase that inhibits the Aβ deposition is the ADAM10, which is altered in the blood and cerebrospinal fluid (CSF) of older adults with AD.MethodTo assess whether the levels of ADAM10 forms are altered in CSF of AD and non‐dementia control (NDC) individuals with different APOE genotype, we analysed a total of 13 samples from NDC (mean age = 66.3 ±9.8; T‐tau = 305 ±135 ng/L; Aβ42 = 780 ±253 ng/L) and 41 from AD (mean age 77.0 ±6.2; T‐tau = 845 ±356.1 ng/L; Aβ42 = 456 ± 66 ng/L), subdivided into NDC APOE ε3/ε3 (n = 8), NDC APOE ε3/ε4 (n = 5), AD APOE ε3/ε3 (n = 13), AD APOE ε3/ε4 (n = 14) and AD APOE ε4/ε4 (n = 14). ADAM10 was characterized in human CSF samples by western blotting.ResultAn antibody raised against to the ectodomain region of ADAM10, common to all species, recognized three bands, which might be the proADAM10 (immature form retaining the prodomain), ADAM10f (mature unprocessed full‐length form) and sADAM10 (truncated fragment). Regarding proADAM10, no differences were found among NDC with different APOE genotype. However, the AD APOE ε4/ε4 showed a reduction, which was significantly lower than AD APOE ε3/ε3 (p = 0.0011), NDC APOE ε3/ε3 (p = 0.0460) and NDC APOE ε3/ε3 (p = 0.0012), suggesting the impact of being homozygous for APOE ε4 allele on proADAM10 levels. In the ADAM10f and sADAM10, we observed similar findings. For both species of protein, AD groups carriers of APOE ε4 allele, that is, AD APOE ε3/ε4 and AD APOE ε4/ε4, presented significant lower levels of ADAM10f compared with both non‐carriers subgroups (AD APOE ε3/ε3 and NDC APOE ε3/ε3).ConclusionThe results indicated that being a carrier of the APOE ε4 allele and having developed AD are associated with lower levels of ADAM10f and sADAM10. This study contributes to a better understanding the impact of apoE on the disease.

The influence of Apolipoprotein E ε4 carrier status on posterior cingulate cortex thickness and learning

AbstractBackgroundThinning of the posterior cingulate cortex (PCC) is implicated in Alzheimer’s disease (AD). Though some evidence suggests ApolipoproteinE (APOE) ε4 carriers (ε4+) have thinner PCCs than non‐carriers (ε4‐), the evidence is conflicting and lacks association with learning outcomes relevant to AD.MethodA subset from an ongoing clinical trial (NIH/NIA: R01AG058919) was used for analyses and included 26 ε4+ (73% female, Agemean=55.81±5.53) and 42 ε4‐ (88% female, Agemean= 57.54±5.10), who were all cognitively normal, sedentary, and had a family history of AD. Genetic sampling was completed via passive drool. Structural MRI was completed to assess PCC cortical thickness, and the Rey Auditory Verbal Learning Task (AVLT) was used to assess learning. Brain segmentation was completed with Freesurfer’s automated pipeline, and left and right PCC cortical thickness was extracted for analysis. A learning over trials (LOT) composite score from the AVLT was calculated to represent learning. An analysis of covariance was completed to assess the effect of carrier status on left/right PCC thickness, controlling for age and sex. Linear regressions were completed to assess main effects and interaction of carrier status and left/right PCC thickness in predicting LOT when controlling for age and sex.Resultε4+ had less cortical thickness in the left PCC (F(1,64)=5.07, p=.03), but not the right PCC (p=.33), relative to ε4‐. Carrier status predicted LOT (Left: F(1,62)=10.37, p&lt;.01; Right: F(1,62)=10.66, p&lt;.01), however this was superseded by significant interactions between carrier status and PCC thickness predicting LOT (Left: F(1,62)=10.72, p&lt;.01; Right: F(1, 62)=11.10, p&lt;.01), with post‐hoc analyses demonstrating PCC thickness predicts LOT for ε4+ (Left:β=‐21.07, p=.04; Right:β=‐24.33, p&lt;.01), but not ε4‐ (p’s&gt;.09).ConclusionIn cognitively normal sedentary adults with a family history of AD, carrying the APOE ε4 allele was associated with a thinner left PCC. Further, thinner bilateral PCCs in ε4+ were associated with greater learning during the AVLT task. This suggests that ε4+ may have compensatory neural pathways to account for losses in the PCC, which temporarily bolster learning to delay the onset of AD. However, additional research is needed to continue understanding the neural mechanisms affected by carrying the APOE ε4 allele.

Excessive Visit-to-Visit Small and Dense Low-Density Lipoproteins Elevate Cerebral Small Vessel Disease Progression Risk in the Elderly.

ObjectiveSmall and dense low-density lipoprotein (sdLDL) elevation may be among the most sensitive early biomarkers for nascent cardiovascular disease. This study, therefore, investigated the association between visit-to-visit changes in sdLDL and cerebral small vessel disease (CSVD) progression in older individuals, and the influence of Apolipoprotein E (APOE) genotype on this association.MethodsBetween April 2007 and July 2009, 1,143 participants ≥60 years old were recruited from the Shandong region of China, and sdLDL was measured at baseline and at each follow-up visit. White matter hyperintensities (WMHs), lacunes, microbleeds, and enlarged perivascular spaces (EPVSs) were assessed by magnetic resonance imaging. The APOE genotype was determined and participants were stratified as ε4-positive or ε4-negative.ResultsDuring an average follow-up of 86.0 months, 225 participants (19.7%) developed WMH progression, 193 (16.9%) lacune progression, 170 (14.9%) microbleed progression, and 185 (16.2%) EPVS progression. Compared with patients in the first (lowest) tertile of visit-to-visit mean sdLDL, those in the second and third tertiles demonstrated significantly greater risks of WMH progression (53.5 and 105.3% higher), lacune progression (53.3 and 60.8%), microbleed progression (47.2 and 127.6%), and EPVS progression (54.0 and 135.0%) after adjustment for confounders (all adjusted P values for trends <0.001). Compared with patients in the first tertile of visit-to-visit sdLDL SD, those in the second and third tertiles also demonstrated significantly greater risks of WMH progression (49.9% and 143.6%), lacune progression (75.3 and 178.0%), microbleed progression (12.7 and 64.7%), and EPVS progression (41.7 and 114.6%) after adjustment (all P < 0.001). There were significant and positive visit-to-visit mean sdLDL × visit-to-visit sdLDL SD, visit-to-visit mean sdLD×ε4-positive, visit-to-visit sdLDL SD×ε4-positive, and visit-to-visit mean sdLDL×visit-to-visit sdLDL SD×ε4-positive interactions influencing CSVD progression after confounder adjustment (all P < 0.05).ConclusionLarge and variable visit-to-visit changes in sdLDL are independent predictors of aggressive CSVD progression, and this association is strongly influenced by APOE ε4 allele genotype.

Concordance of Alzheimer's Disease Subtypes Produced from Different Representative Morphological Measures: A Comparative Study.

Background: Gray matter (GM) density and cortical thickness (CT) obtained from structural magnetic resonance imaging are representative GM morphological measures that have been commonly used in Alzheimer’s disease (AD) subtype research. However, how the two measures affect the definition of AD subtypes remains unclear. Methods: A total of 180 AD patients from the ADNI database were used to identify AD subgroups. The subtypes were identified via a data-driven strategy based on the density features and CT features, respectively. Then, the similarity between the two features in AD subtype definition was analyzed. Results: Four distinct subtypes were discovered by both density and CT features: diffuse atrophy AD, minimal atrophy AD (MAD), left temporal dominant atrophy AD (LTAD), and occipital sparing AD. The matched subtypes exhibited relatively high similarity in atrophy patterns and neuropsychological and neuropathological characteristics. They differed only in MAD and LTAD regarding the carrying of apolipoprotein E ε2. Conclusions: The results verified that different representative morphological GM measurement methods could produce similar AD subtypes. Meanwhile, the influences of apolipoprotein E genotype, asymmetric disease progression, and their interactions should be considered and included in the AD subtype definition. This study provides a valuable reference for selecting features in future studies of AD subtypes.

Influence of apolipoprotein A-I and B genetic variations on insulin resistance, metabolic syndrome in obstructive sleep apnea

Influence of apolipoprotein A-I and B genetic variations on insulin resistance, metabolic syndrome in obstructive sleep apnea

Abstract 17: Apolipoprotein E and Intracerebral Hemorrhage: A Trans-Ethnic Meta-Analysis

Introduction: Risk of lobar and non-lobar intracerebral hemorrhage (ICH) varies among blacks, whites and Hispanics. We sought to determine whether these differences could be due to variability in the effects of Apolipoprotein E (APOE) epsilon (ε) alleles, the most potent genetic risk factor for ICH. Methods: Primary ICH cases and controls were collected from US and European sites contributing to the International Stroke Genetic Consortium (ISGC). We meta-analyzed the effects of APOE allele status on ICH risk applying a two-stage clustering approach based on race/ethnicity and the contributing study. Models were adjusted for age, sex, history of hypertension, hypercholesterolemia, warfarin, statin and antiplatelet use, smoking and alcohol use. A propensity score analysis was used to model the influence of APOE against the burden of hypertension across races/ethnicities. Results: 13,124 subjects (54.5% male, median age 66 years) were included. In whites, APOE ε2 (odds ratio (OR)=1.85, 95% confidence interval (CI)=1.27-2.69, p&lt;0.001) and APOE ε4 (OR=1.94, 95% CI=1.58-2.38, p&lt;0.001) were independently associated with lobar ICH risk, however within self-identified Hispanics and blacks, no associations were found (Figure). After propensity score-matching for hypertension burden, APOE ε4 was associated with lobar ICH risk among whites (OR=1.12, 95% CI=1.08-1.17) and Hispanics (OR=1.07, 95% CI=1.01-1.15, p=0.01), but not blacks (OR=1.02 95% CI=0.98-1.07, p=0.251). APOE ε2 and ε4 did not show an effect on non-lobar ICH risk in any race/ethnicity. Conclusion: APOE ε4 and ε2 alleles affect lobar ICH risk variably by race and ethnicity. Associations are confirmed in whites but can be shown in Hispanics only when the excess burden of hypertension is propensity score-matched. Further studies are needed to explore interactions between APOE alleles and environmental exposures that vary by race and ethnicity in representative populations at risk for ICH.

Influence of Apolipoprotein A-I and B Genetic Variations on Insulin Resistance and Metabolic Syndrome in Obstructive Sleep Apnea

Background: Both apolipoprotein A-I (APOA-I) and apolipoprotein B (APOB) are associated with insulin resistance, metabolic syndrome (MetS), and obstructive sleep apnea (OSA). However, whether multiple single nucleotide polymorphism (SNP) variants of APOA-I and APOB exert a collaborative effect on insulin resistance and MetS in OSA remains uncertain. Methods: Initially, 12 APOA-I SNPs and 30 APOB SNPs in 5,259 subjects were examined. After strict screening, four APOA-I SNPs and five APOB SNPs in 4,007 participants were included in this study. For each participant, the genetic risk score (GRS) was calculated based on the cumulative effect of multiple genetic variants of APOA-I and APOB. Logistic regression analyses were used to evaluate the relationships between APOA-I/APOB genetic polymorphisms, insulin resistance, and MetS. Results: Patients with insulin resistance had a lower APOA-I GRS and higher APOB/APOA-I and APOB levels after adjustments [odds ratio (OR) = 0.917, P = 0.001; OR = 2.285, P < 0.001; OR = 3.168, P < 0.001, respectively]. Individuals with MetS had a lower APOA-I GRS and APOA-I level and higher APOB/APOA-I and APOB levels after adjustments (OR = 0.870, 0.09, 14.488, 6.098, respectively, all P < 0.001). In addition, individuals in the top quintile of the APOA-I genetic score distribution had a lower risk of insulin resistance and MetS after adjustments (OR = 0.761, P = 0.007; OR = 0.637, P < 0.001, respectively). Conclusion: In patients with OSA, APOA-I genetic variation contributes to insulin resistance and MetS, whereas APOB genetic variation contributes to MetS only. Funding Statement: National Key RD National Natural Science Foundation of China (81770987, 81700896, 81701306, 81770988); Innovation Program of Shanghai Municipal Education Commission (2017-01-07-00-02-E00047); multi-center clinical research project from school of medicine, Shanghai Jiao Tong University (DLY201502) and Shanghai Shen-Kang Hospital Management Center Project (SHDC12015101). Declaration of Interests: The authors declare that they have no competing interests. Ethics Statement Approval: The ethics committee of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital approved this study according to Helsinki Declaration II. All the participants have given the informed consent before taking part in the study.

Influence of APOE and RNF219 on Behavioral and Cognitive Features of Female Patients Affected by Mild Cognitive Impairment or Alzheimer's Disease.

The risk for Alzheimer’s disease (AD) is associated with the presence of the 𝜀4 allele of Apolipoprotein E (APOE) gene and, recently, with a novel genetic variant of the RNF219 gene. This study aimed at evaluating interactions between APOE-𝜀4 and RNF219/G variants in the modulation of behavioral and cognitive features of two cohorts of patients suffering from mild cognitive impairment (MCI) or AD. We enrolled a total of 173 female MCI or AD patients (83 MCI; 90 AD). Subjects were screened with a comprehensive set of neuropsychological evaluations and genotyped for the APOE and RNF219 polymorphic variants. Analysis of covariance was performed to assess the main and interaction effects of APOE and RNF219 genotypes on the cognitive and behavioral scores. The analysis revealed that the simultaneous presence of APOE-𝜀4 and RNF219/G variants results in significant effects on specific neuropsychiatric scores in MCI and AD patients. In MCI patients, RNF219 and APOE variants worked together to impact the levels of anxiety negatively. Similarly, in AD patients, the RNF219 variants were found to be associated with increased anxiety levels. Our data indicate a novel synergistic activity APOE and RNF219 in the modulation of behavioral traits of female MCI and AD patients.

Apolipoprotein B and angiotensin-converting enzyme polymorphisms and aerobic interval training: randomized controlled trial in coronary artery disease patients.

Physical training has been strongly recommended as a non-pharmacological treatment for coronary artery disease (CAD). Genetic polymorphisms have been studied to understand the biological variability in response to exercise among individuals. This study aimed to verify the possible influence of apolipoprotein B (ApoB: rs1042031 and rs693) and angiotensin-converting enzyme (ACE-ID: rs1799752) genotypes on the lipid profile and functional aerobic capacity, respectively, after an aerobic interval training (AIT) program in patients with CAD and/or cardiovascular risk factors. Sixty-six men were randomized and assigned to trained group (n=32) or control group (n=34). Cardiopulmonary exercise test was performed to determine the ventilatory anaerobic threshold (VAT) from cardiorespiratory variables. The AIT program, at an intensity equivalent to %VAT (70–110%), was conducted three times a week for 16 weeks. ApoB gene polymorphisms (−12669C>T (rs1042031) and −7673G>A (rs693)) were identified by real-time polymerase chain reaction (PCR). I/D polymorphism in the ACE gene (rs1799752) was identified through PCR and fragment size analysis. After 16 weeks, low-density lipoprotein (LDL) levels increased in the trained and control groups with the GA+AA genotype (−7673G>A) of the ApoB gene. Trained groups with ACE-II and ACE-ID genotypes presented an increase in oxygen consumption (VO2VAT) and power output after the AIT program. The presence of the ACE I-allele was associated with increased aerobic functional capacity after the AIT program. Increased LDL levels were observed over time in patients with the −7673G>A polymorphism of the ApoB gene. Trial Registration Information: ClinicalTrials.gov: NCT02313831

Influence of Apolipoprotein E on the Lipid Profile and Postprandial Triglyceride Levels in Brazilian Postmenopausal Women With Artery Disease.

This study confirms the association of risk factors for coronary artery disease (CAD) and the apoE polymorphisms, specifically related to the APOE*4 allele, with coronary disease in postmenopausal women. Significantly altered values of the lipid profile were found in patients when compared with controls, independent of the presence of the APOE*4 allele. However, the controls showed higher high-density lipoprotein cholesterol (HDL-C) levels and reduced triglyceride (TG) levels, differing significantly from patients. In this case, the study of subgroups, considering the APOE*3/3 and APOE*3/4 genotypes, suggests that the APOE*4 allele is not implicated in the variations of the lipid profile of patients and determined an increase in the production levels of HDL-C and a reduction in TG highly benefiting the control group compared with APOE*3/3 genotype. The metabolic kinetics of TG, although with the same pattern between groups, and the presence of the APOE*4 allele are suggested to be associated with accelerated clearance compared with APOE*3 allele in non-CAD group.

Cognition, brain atrophy, and cerebrospinal fluid biomarkers changes from preclinical to dementia stage of Alzheimer's disease and the influence of apolipoprotein e.

Knowledge of Alzheimer's disease (AD) manifestation in the pre-dementia stage facilitates the selection of appropriate measures for early detection and disease progression. To examine the trajectories of cognitive performance, gray matter volume (GMV), and cerebrospinal fluid (CSF) biomarkers, together with the influence of apolipoprotein E (APOE) in subjects with amyloid-β (Aβ) deposits across the pre-clinical to dementia stages of AD. 356 subjects were dichotomized into Aβ+ and Aβ- groups based on their CSF Aβ1-42 level. We derived AD-related atrophic regions (AD-ROIs) using the voxel-based morphometry approach. We characterized the trajectories of cognitive scores, GMV at AD-ROIs, and CSF biomarkers from preclinical to disease stages in Aβ+ subjects. The effect of APOE ε4 genotype on these trajectories was examined. Impairments in executive functioning/processing speed (EF/PS) and atrophy at the right supramarginal/inferior parietal gyrus were detected in cognitively normal Aβ+ subjects. Together with the APOE ε4 carrier status, these measures showed potential to identify cognitively normal elderly with abnormal CSF Aβ1-42 level in another independent cohort. Subsequently, impairment in memory, visuospatial, language, and attention as well as atrophy in the temporal lobe, thalamus, and mid-cingulate cortex were detectable in Aβ+ mild cognitive impairment (MCI) subjects. In MCI and dementia Aβ+ subjects, ε4 carriers had more severe atrophy of the medial temporal lobe and memory impairment but higher EF/PS compared to non-carriers. EF/PS decline and right parietal atrophy might act as non-invasive screening tests for abnormal amyloid deposition in cognitively normal elderly. APOE modulation on subsequent trajectories in cognition and atrophy should be taken into account when analyzing disease progression.

Laminar distribution of β-amyloid (Aβ) peptide deposits in the frontal lobe in familial and sporadic Alzheimer's disease.

To determine whether genetic factors influence frontal lobe degeneration in Alzheimer's disease (AD), the laminar distributions of diffuse, primitive, and classic β-amyloid (Aβ) peptide deposits were compared in early-onset familial AD (EO-FAD) linked to mutations of the amyloid precursor protein (APP) or presenilin 1 (PSEN1) gene, late-onset familial AD (LO-FAD), and sporadic AD (SAD). The influence of apolipoprotein E (Apo E) genotype on laminar distribution was also studied. In the majority of FAD and SAD cases, maximum density of the diffuse and primitive Aβdeposits occurred in the upper cortical layers, whereas the distribution of the classic Aβ deposits was more variable, either occurring in the lower layers, or a double-peaked (bimodal) distribution was present, density peaks occurring in upper and lower layers. The cortical layer at which maximum density of Aβ deposits occurred and maximum density were similar in EO-FAD, LO-FAD and SAD. In addition, there were no significant differences in distributions in cases expressing Apo E ε4 alleles compared with cases expressing the ε2 or ε3 alleles. These results suggest that gene expression had relatively little effect on the laminar distribution of Aβ deposits in the frontal lobe of the AD cases studied. Hence, the pattern of frontal lobe degeneration in AD is similar regardless of whether it is associated with APP and PSEN1, mutation, allelic variation in Apo E, or with SAD.

Source analysis of spontaneous magnetoencephalograpic activity in healthy aging and mild cognitive impairment: influence of apolipoprotein E polymorphism.

The apolipoprotein E (APOE) ε4 allele is a genetic risk factor for the development of late-onset Alzheimer's disease (AD), which affects cholinergic system functioning. The association between reduced cholinergic levels and increase of magnetoencephalographic (MEG) low-frequency has been used to explain spectral changes found in AD patients. However, the investigation in predementia stages is scarce. We obtained MEG recordings from 25 aged controls and 36 mild cognitive impairment (MCI) patients during a resting-state condition. According to their APOE genotype, MCIs and controls were subdivided in carriers and non-carriers of the ε4 allele. Sources of spectral variations in these groups were calculated through beamforming. MCI patients exhibited a significant increase of relative power within the low-frequency domain, accompanied by a power decrease within the high-frequency range. APOEε4 carriers showed an increased relative power in the 4.5-6.5 Hz frequency range over frontal lobes. The power increase observed in controls carrying ε4 was significantly higher as compared with MCI non-carriers, while MCI carriers exhibited the highest relative power within the 4.5-6.5 Hz range. Higher power values within the low-frequency ranges correlated with a poorer cognitive performance in MCIs and controls. Our investigation demonstrates that APOEε4 affects resting-state activity to an extent that makes it more proximate to the pattern observed in early stages of AD. Therefore, a combination of genetic and neurophysiological information might help to detect MCI patients at higher risk of conversion to AD, and asymptomatic subjects at higher risk of developing a manifest cognitive deterioration.

Sex dependent influences of apolipoprotein E on the expression ATP-binding cassette transporters during experimental autoimmune encephalomyelitis

Sex dependent influences of apolipoprotein E on the expression ATP-binding cassette transporters during experimental autoimmune encephalomyelitis

Higher apolipoprotein B levels are associated with earlier onset of first-ever atherosclerotic stroke

Background: Many studies have revealed apolipoproteins are risk factors for ischemic stroke, but the influence of apolipoproteins on onset age of first-ever atherosclerotic stroke has not been well investigated. Methods: We recruited 357 qualified participants from consecutive patients with acute ischemic stroke who came to the stroke registry center in Sichuan Provincial People's Hospital, Chengdu, China. Patients were stratified into tertiles according to the distributions of apoB levels for large artery atherosclerosis (LAA) and small artery atherosclerosis (SAA) groups. The onset age of stroke was analyzed tripartitely in terms of early-onset group, the middling-onset group and the late-onset group. Multinomial logistical regression was used to analyze the associations between the two. Results: The risk of early-onset stroke increased monotonically with higher apoB levels (the second tertile, adjusted OR = 2.61, 95% CI 1.18–5.79 (p = 0.018); the third tertile, adjusted OR = 19.52, 95% CI 5.93–64.31 (p < 0.001)), and patients with the highest tertile of apoB levels had a 9.20 times (95% CI, 2.97–28.53, p < 0.001) increased risk of middling-onset stroke in reference to late onset of stroke. Conclusions: The present study suggests the higher the apolipoprotein B levels are, the earlier an atherosclerotic stroke might occur in a Chinese population.

Influence of apolipoprotein E, age and aortic site on calcium phosphate induced abdominal aortic aneurysm in mice

ObjectiveTo assess relevant features of abdominal aortic aneurysms (AAA) induced by calcium phosphate within a mouse model. Specifically we investigated: (1) whether apolipoprotein E deficiency and older age promoted AAA formation, and (2) whether the local application of calcium phosphate affected the size of distant aortic segments. MethodsAAA was induced by application of calcium phosphate to the infra-renal aortas of 3 and 7 month old male mice. AAA induction was assessed by calculating expansion of the infra-renal aortic diameter over 1–4 weeks. Aortic samples were assessed to quantify calcification, macrophages infiltration, elastic lamellar degradation and apoptosis. Blood pressure was measured by the tail cuff method, and plasma concentrations of total cholesterol, low density lipoprotein and very low density lipoprotein cholesterol, and pro-inflammatory cytokines were measured using commercially available kits. The maximum diameters of the aortic arch, thoracic and supra-renal aorta at sacrifice were measured by morphometry and the mean maximal diameter of these three aortic segments was calculated. ResultsThe median expansion of the infra-renal aorta 2 weeks after AAA induction was significantly greater in apolipoprotein E deficient (ApoE−/−) mice than in age- and gender-matched wild type controls [275.8% (IQR 193.8%–348.5%) versus 94.7% (IQR 47.8%–163.4%), P = 0.02]. The greater aortic expansion in ApoE−/− mice was associated with aortic calcification, macrophage infiltration, elastic lamellar degradation and apoptosis of cells in the media and adventitia. The plasma low density lipoprotein/very low density lipoprotein cholesterol concentrations 2 weeks after AAA induction were positively correlated with the expansion of the infra-renal aorta induced by calcium phosphate. The median expansion of the infra-renal aorta 2 weeks after AAA induction was similar in 3 and 7 month old wild type mice. The local administration of calcium phosphate was associated with an increase in the mean maximal diameter of distant aortic segments, but not associated with changes in the concentrations of pro-inflammatory markers in either the plasma or the spleen. ConclusionThis study suggests that apolipoprotein E deficiency, but not age, predisposes to AAA induced within the calcium phosphate model. Increased AAA expansion in ApoE−/− mice was associated with calcification, macrophage infiltration, elastic lamellar degradation, and cell apoptosis. Local application of calcium phosphate also promoted dilation of distant aortic segments.

Influence of apolipoprotein E gene polymorphism on development of type 2 diabetes mellitus in Chinese Han population: A meta-analysis of 29 studies

ObjectivesPublished data regarding the association between apolipoprotein E (ApoE) gene polymorphism and type 2 diabetes mellitus (T2DM) risk in Chinese Han population were inconclusive. To derive a more precise estimation of the relationship between this variant and T2DM risk in Chinese Han population, we performed this meta-analysis. Design and methodsA computerized literature search was conducted to identify the relevant studies from PubMed, EMbase, Web of Science, CBMdisc, CNKI, and Google Scholar. Additionally, hand searching of the references of identified articles was performed. All the statistical tests were performed using Stata 11.0. ResultsA total of 29 articles with 4615 T2DM cases and 2867 controls were included in the present meta-analysis. The results showed evidence for significant association between ApoE gene polymorphism and T2DM risk (for ε2/ε3 vs. ε3/ε3: OR=1.37, 95% CI=1.12–1.68, P<0.01; for ε3/ε4 vs. ε3/ε3: OR=1.53, 95% CI=1.23–1.91, P<0.01; for ε4/ε4 vs. ε3/ε3: OR=1.86, 95% CI=1.22–2.84, P<0.01; for ε2 allele vs. ε3 allele: OR=1.28, 95% CI=1.08–1.52, P=0.01; for ε4 allele vs. ε3 allele: OR=1.43, 95% CI=1.22–1.68, P<0.01). In addition, significant association was also found between ApoE gene polymorphism and diabetic nephropathy (DN) risk. ConclusionsThe results of this meta-analysis suggest that the ApoE ε2 and ε4 alleles may be associated with increased risks of T2DM and DN in Chinese Han population. Additional well-designed genome-wide association studies are required to confirm these results.

The influence of Apolipoprotein E genotype on regional pathology in Alzheimer’s disease

BackgroundCarriers of the ApoE ϵ4 allele are at a greater risk for developing Alzheimer’s disease (AD) and those who do develop AD tend to have a much greater neuropathological disease burden. Although several studies have shown significant differences in AD pathology among ϵ4 carriers and non-carriers, few have characterized these differences in terms of brain region and neuropathological score frequency.Methods566 pathologically-confirmed AD cases who were followed prospectively with antemortem dementia diagnoses (312 ApoE ϵ4 carriers and 254 ApoE ϵ4 non-carriers) were compared on the frequencies of neuropathological frequency scores (none, sparse, moderate, frequent) among several different brain regions (frontal, temporal, parietal, hippocampal, and entorhinal) using the CERAD scoring system. Pathology score frequencies were analyzed by carrier status (ϵ4 carrier vs. ϵ4 non-carrier) and by genotype (2/3, 3/3, 2/4, 3/4, 4/4). Both analyses investigated pathology score frequencies among different brain regions (frontal, temporal, parietal, hippocampal, and entorhinal).Resultsϵ4 carriers had a significantly lower age at death (p <0.001) and significantly higher Braak scores (p <0.001) than ϵ4 non-carriers. Genotype comparison revealed that plaque and tangle pathologies increased in the following pattern, 2/3<3/3<2/4<3/4<4/4, for several brain regions. When stratified by age and ApoE ϵ4 carrier status, ϵ4 carriers tended to have significantly more frequent scores across most cortical areas. However, non-carriers age 90 and older tended to have greater plaque pathology than carriers. For tangle pathology, ϵ4 carriers tended to have significantly more “frequent” scores than non-carriers, except for the hippocampal and entorhinal areas in individuals age 90 and older.ConclusionsApoE ϵ4 carriers had a significantly higher percentage of “frequent” scores for plaques and tangles when compared to ApoE ϵ4 non-carriers for several brain regions. However, ϵ4 non-carriers age 90 and older tended to have less plaque and tangle pathology in certain brain regions. These results demonstrate that AD pathology may manifest itself differently based on ApoE genotype and suggest that ApoE carriers and non-carriers may have different patterns of AD neuropathology location and density.