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APOe is associated with disease progression in various conditions. Abbreviation: APOe, apolipoprotein e. 

APOe is associated with disease progression in various conditions. Abbreviation: APOe, apolipoprotein e. 

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Apolipoprotein E (APOE) is a lipid-transport protein abundantly expressed in most neurons in the central nervous system. APOE-dependent alterations of the endocytic pathway can affect different functions. APOE binds to cell-surface receptors to deliver lipids and to the hydrophobic amyloid-β peptide, regulating amyloid-β aggregations and clearances...

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... structural differences in APOE isoforms helped establish the molecular mechanism responsible for the associated pathology. Defects in APOE could result in alterations in its structure and function. 33 The critical effect of APOE in regulating plasma lipid and lipoprotein levels has been extensively and carefully studied. 3,13,[33][34][35][36][37] Evidence indicates its association with neurodegenerative diseases and also other chronic diseases. This review will summarize the critical available data related to APOE defects and their role in AD, PD, CVD, type III HLP, MS, T2DM, VD, and IS ( Figure ...

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... APOE has two polymorph sites: Cys112 and Arg158. Their mutations could result in three main alleles of APOE: E2 (Cys112, Cys112), E3 (Cys112, Arg158), and E4 (Arg158, Arg158), and their heterozygous combinations (12,13). The level of Aß42 in the cerebrospinal fluid determines the onset of preclinical AD and is associated with a strong predictive marker of cognitive decline in normal subjects (14)(15)(16)(17), whereas total-tau and phosphorylated-tau are late-onset markers of AD (18). ...
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Apolipoprotein (APOE) is implicated and verified as the main risk factor for early-onset Alzheimer's disease (AD). APOE is a protein that binds to lipids and is involved in cholesterol stability. Our paper reports a case of a sporadic early-onset AD (sEOAD) patient of a 54-year-old Korean man, where a novel APOE Leu159Pro heterozygous mutation was revealed upon Whole Exome Sequence analysis. The proband's CSF showed downregulated levels of Aβ42, with unchanged Tau levels. The mutation is in the Low-Density Lipoprotein Receptor (LDLR) region of the APOE gene, which mediates the clearance of APOE lipoproteins. LDLR works as a high-affinity point for APOE. Studies suggest that APOE-LDLR interplay could have varying effects. The LDLR receptor pathway has been previously suggested as a therapeutic target to treat tauopathy. However, the APOE-LDLR interaction has also shown a significant correlation with memory retention. Leu159Pro could be an interesting mutation that could be responsible for a less damaging pattern of AD by suppressing tau-association neurodegeneration while affecting the patient's memory retention and cognitive performance.
... These mutations, identified in familial AD (FAD), alter APP and lead to the overproduction of a longer, toxic version of Aβ42. The APOE gene (located at 19q13.2) encodes a glycoprotein (34kDa) that is composed of 299 amino acids (apoE) and is associated with low-density lipoproteins (LDL), very-low-density lipoproteins VLDL and high-density lipoproteins (HDL) [7]. In the CNS, ApoE mediates the neuronal delivery of cholesterol which is an essential component for axonal growth, synaptic formation and remodeling events that are crucial for learning, memory formation and neuronal repair. ...
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Alzheimer’s disease (AD) is the most common cause of dementia worldwide. The clinical spectrum of suspected AD has been extended from mild cognitive impairment (MCI) to preclinical AD which includes people who have typical cognitive function but harbor the underlying biological features of AD. We report the first case of an Italian patient affected by MCI (MMSE 24\30), characterized by a double mutation p.Lys311Arg (K311R) and p.Glu318Gly (E318G) in Presenilin-1 but with the absence of abnormal accumulation of amyloid beta.
... The polymorphism in the APOE is reported to be associated with many CNS disorders including, Alzheimer's Disease (AD), Intracerebral Hemorrhage (ICH), Traumatic Brain Injury (TBI), Vascular Dementia (VD), Multiple Sclerosis (MS), Stroke, and many more in the list (Van Giau et al., 2015). Interest in APOE with regards to CNS escalated greatly when in 1991, APOE immunoreactivity was first reported in amyloid plaque (Namba and Ikeda, 1991), and subsequently, in 1993, APOE ε4 allele was reported as a risk factor for AD (Corder et al., 1993). ...
... In some neurodegenerative disorders (NDs), the other isoforms of the APOE also possess as a risk factor, like in the case of PD, where studies suggested that APOE ε2 increase the risk instead of the APOE ε4 (studies are also in favor of APOE ε4 as well) (Huang et al., 2004). However, in most of the NDs, APOE ε4 is considered as a risk factor where it contributes to the disease pathology by the various mechanisms, including increased oxidative stress and inflammatory response, reduced vascular functions, and levels of growth factor (VEGF, BDNF), decrease in neuronal and synaptic functions as well as energy disbalance (Van Giau et al., 2015). Recent evidence suggests that ApoE induces the neurodegenerative phenotype of microglia (MGnD) that has pro-inflammatory and phagocytotic functions in NDs. ...
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The prevalence and burden of CNS disorders are increasing significantly due to the increase in life span and population. The contemporary need in CNS drug discovery is to develop the therapy that can halt the disease progression (disease-modifying therapy). While developing such CNS therapies, the major bottleneck is the blood-brain barrier (BBB) impermeability of drugs that influences the development of effective therapies to treat various CNS disorders. Since the influential innovation of insulin to treat diabetic patients in the 1920s, a lot of attention has been given for producing therapeutic proteins and peptides as remedies for several diseases, including neurological disorders. Recently, researchers have explored therapeutic potential of apolipoprotein E (ApoE) derived peptides in the same context. ApoE is the major apolipoprotein produced in the brain by the astrocytes and plays a significant role in the formation of synapses, myelination, and neuronal proliferation. ApoE can be a potential candidate for treating CNS disorders. However, the large size of the ApoE leads to the BBB impermeability that knockout its use in native form. This problem can be overcome by developing small ApoE-derived peptides with good BBB permeability and similar biological function as native ApoE. Various ApoE mimetics peptides have been developed and investigated in different CNS disorders. This review provides insights into the latest development of ApoE and its mimetic peptides in CNS disorders, along with their beneficial outcomes.
... These are further confirmed in this study. The 2 and 4 allele frequencies in the cohort are 2.0% and 24.0%, respectively, which are lower and higher than those in Chinese general population (10.5%, 7.1%) [21]. Besides, we find the rs7412-T allele is relevant to increased CSF A␤ 42 level, and the rs429358-C allele shows a trend associated with decreased A␤ 42 . ...
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Background: The previous studies have identified several genes in relation to Alzheimer's disease (AD), such as ABCA7, CR1, etc. A few studies have explored the association between the common variants, mainly in the non-coding regions of these genes, and cerebrospinal fluid (CSF) biomarkers. Fewer studies target the variants in the coding regions. Objective: To illustrate the association between the common variants within or adjacent to the coding regions of AD susceptible genes and CSF biomarkers in AD patients. Methods: 75 sporadic probable AD patients were extracted from the dementia cohort of Peking Union Medical College Hospital. They all had history inquiry, physical examination, blood test, cognitive assessment, brain MRI, CSF testing of Aβ42, 181p-tau, and t-tau, and next-generation DNA sequencing. Sixty-nine common single nucleotide polymorphisms (SNPs) (minor allele frequency > 0.01) within or near the coding region of 13 AD susceptible genes were included in the analysis. Results: The rs7412-CC (APOE) genotype showed lower CSF Aβ42 level and higher p-tau/Aβ42 ratio than the rs7412-CT genotype. The rs3752246-C (ABCA7) allele correlated with lower CSF Aβ42 level. The alternate alleles of six ABCA7 SNPs were related to lower CSF p-tau, including rs3745842, rs3764648, rs3764652, rs4147930, rs4147934 and rs881768. The rs11609582-TT (A2M) genotype showed higher CSF p-tau than the rs11609582-TA genotype. The p-tau/Aβ42 ratio was higher in the rs490460-TT (BACE1) genotype relative to the rs490460-GT genotype. Conclusion: Some common variants within or near the coding regions of APOE, ABCA7, A2M, and BACE1 are associated with CSF Aβ42, p-tau. or p-tau/Aβ42.
... Being an ε4 carrier has been recognized as the main genetic risk factor associated with the development of late-onset AD. 8 The percentage distribution of the isoforms described in the literature for the alleles of the APOΕ gene is 79% for the ε3 allele, 13.3% for the ε4 allele, and 7.3% for the ε2 allele. 27,28 The genotype frequencies of the APOΕ gene in our sample studied were similar to those described in Colombian, Latin American, and world literature. 26 A hazard ratio (HR) of 1.35 (95%CI 1.00-1.83) ...
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Being an ϵ4 carrier in the Apoϵ gene has been suggested as a modifying factor for the interaction between cardio-metabolic, social risk factors, and the development of cognitive impairment. Objective: The main objective of this study was to assess the existence of such interaction in a sample of Bogota's elderly population. Methods: A cross-sectional study was conducted with 1,263 subjects older than 50 years. Each participant was diagnosed by consensus, after neuropsychological and neuropsychiatric evaluations, under a diagnosis of normal cognition, mild cognitive impairment (MCI) according to Petersen's criteria, or dementia according to DSM-IV criteria. Apoϵ was typified and an analysis of MoCA test was performed in each group carrying or not ϵ4 allele. Results: Our study showed that 75% were women with a median age of 68 years (interquartile range 62-74 years) and a median schooling for 6 years (interquartile range 4-12 years). Dementia was related to low education level of ≤5 years OR=11.20 (95%CI 4.99-25.12), high blood pressure (HBP) OR=1.45 (95%CI 1.03-2.05), and age over 70 years OR=7.68 (95%CI 3.49-16.90), independently of being or not an ϵ4 allele carrier. Diabetic subjects with dementia carrying ϵ4 allele showed a tendency to exhibit lower scores on the MoCA test, when compared with noncarriers' diabetic subjects with dementia. Conclusions: The presence of ϵ4 allele does not modify the relationship between cognitive impairment and the different cardio-metabolic and social risk factors, except in diabetic subjects ϵ4 carriers with dementia who showed a tendency to exhibit lower scores of the MoCA test, when compared with noncarriers' diabetic subjects with dementia.
... ApoE3 contains a cysteine residue at position 112 and an arginine residue at position 158 (E3=Cys112/Arg158), whereas ApoE2 has cysteine residues at both positions (E2=Cys112/Cys158), and ApoE4 contains arginine residues at both sites (E4=Arg112/Arg158) (13). ApoE-ϵ4 is a risk factor for a variety of diseases, such as Alzheimer's disease (AD) (14), cardiovascular disease (15), and hyperlipidemia (16). ApoE is a major source of cholesterol precursors for the synthesis of ovarian estrogen and progesterone (13), and a relationship between the serum estrogen level and ApoE exists in human ovarian follicular fluid (FF) (17), which suggests that ApoE might play an important role in the ovary. ...
... Previous studies have shown that ϵ3 is the most abundant ApoE genotype in the human population, with a frequency of 49%-90%, followed by ϵ4 with a frequency of 5%-37%, and ϵ2 was the least abundant genotype, with a frequency of 0%-14% (14). These findings are consistent with our analytical results that showed the proportion of ϵ3 was highest in both the control and EMT groups and that the proportion of ϵ2 in the control group was as low as 1.8%. ...
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More than 10% of women suffer from endometriosis (EMT) during their reproductive years. EMT can cause pain and infertility and requires further study from multiple perspectives. Previous reports have indicated that an increase inapolipoprotein E (ApoE) may be associated with a lower number of retrieved mature oocytes in older women, and an association between ApoE and spontaneous pregnancy loss may exist in patients with EMT. The purpose of this study was to investigate the existence of an increase in ApoE in follicular fluid (FF) and the possible relationship between ApoE and EMT in Chinese women. In the current study, 217 Chinese women (111 control subjects and 106 EMT patients) were included. The ApoE genotypes were identified by Sanger sequencing. We found that ApoE expression in FF was higher in patients with EMT than in the control group. In addition, a significant difference in ApoE4 carriers (ϵ3/ϵ4, ϵ4/ϵ4) was found between the control subjects and the patients with EMT. Furthermore, a nonparametric test revealed significant differences in the numbers of blastocysts and high-quality blastocysts, but not the hormone levels of FSH, LH, and E2, between the two groups. We also established a multifactor (BMI, high-quality blastocysts, and ϵ4) prediction model with good sensitivity for identifying patients who may suffer from EMT. Our results demonstrate that ApoE expression in FF is increased in EMT, the ApoE-ϵ4 allele is significantly linked to EMT, and a combined analysis of three factors (BMI, high-quality blastocysts, and ϵ4) could be used as a predictor of EMT.
... Examination of variations in the AH proteome between disease states as well as between demographic groups may prove helpful in understanding the elusive mechanism(s) of glaucomatous optic neuropathy. Apolipoproteins have been previously established as markers for multiple systemic [18][19][20] and neurodegenerative diseases [21][22][23][24][25], and it has been more recently observed that their levels in AH are altered in the presence of ocular conditions [8,10]. As such, we aimed to probe our large data set for differences in AH apolipoprotein levels between glaucomatous and cataract patients and quantify intra-population variation. ...
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Background Evidence suggests that proteins related to lipid metabolism, such as apolipoproteins, play an important role in the maintenance of normal vision. While several members of the apolipoprotein family are abundant in human aqueous humor (AH), their study remains difficult due to the AH’s small volume, low protein concentration, and the invasive nature of sample collection. In this study, we report the use of Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) to discover associations between AH apolipoproteins and race, gender, and ocular structure in patients with and without primary open angle glaucoma (POAG). Methods AH samples were collected from 231 patients undergoing phacoemulsification or glaucoma incisional surgery at the Medical College of Georgia, Augusta University and subsequently analyzed via LC-MS/MS. The number of peptide spectrum matches (PSMs) for each protein was used as a semi-quantitative measure of relative protein levels. Parameters related to ocular structure were determined using Optical Coherence Tomography (OCT) and Heidelberg Retinal Tomography (HRT). These data sets were probed for relationships between apolipoprotein levels and POAG, demographics (gender and race), and ocular structure. Results A total of ten apolipoproteins were detected in the 231 collected AH samples, with six detected in 100% of the samples, one detected in almost 57% of the samples and three detected in less than 10% of the samples. The levels of APOA1, APOC3, and APOD were higher among POAG subjects. Stratification by gender and race revealed demographic-specific variations. The levels of five apolipoproteins (APOA1, APOA2, APOA4, APOC3, and APOD) were higher in female POAG patients, whereas no apolipoprotein levels were altered in male POAG patients. The levels of APOA1, APOA2, APOA4, and APOD were increased in glaucomatous African American patients, whereas APOE and APOH levels were decreased in glaucomatous Caucasian patients. We also found distinct associations between apolipoprotein levels and OCT and HRT parameters in patients with and without POAG. Conclusions The intra-population variation in apolipoprotein levels highlights the heterogeneity of glaucoma as a disease, suggesting the importance of personalized treatments. Gender and race-specific alterations may be associated with higher risks of POAG in females and members of the African American population.
... It also plays role in the transport of triglyceride, phospholipid, and cholesteryl esters, simply by regulating the binding affinity of these lipoproteins. 27 ApoE is encoded by simple ApoE that has three variants of alleles termed as ε 2 , ε 3, and ε 4 in terms of functionality, 28 and it was found that variant ε 4 plays a role in downregulation of inflammatory cytokines more than ε 3 in the brains of younger Alzheimer patients. 29 It was also reported that cholesterol relates to MS disease as well as ApoE incidence and cerebrospinal fluid levels. ...
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Aim of the Study Multiple sclerosis (MS) is a degenerative disease characterized by autoimmune demyelination in the central nervous system. Yet, underlined genetics or environmental markers are still controversial. The impact of vitamin D and cholesterol on disease activity has been phrased by many studies, however, the data available for the Turkish population is very limited. Here, it is aimed to investigate the effect of vitamin D-related polymorphisms (VDBP and VDR) and cholesterol-related variants of ApoE on Turkish MS patients. Materials & Methods Total DNAs were extracted from peripheral blood samples of fifty-one MS patients and fifty healthy volunteers. rs4588 and rs7041 polymorphisms of VDBP, rs2228570 of VDR, as well as ε2, ε3, and ε4 variants of ApoE, were investigated by RT-PCR. Biochemical parameters which thought to be associated with MS were also measured. Results were evaluated statistically. Results Homozygous mutant genotype and G allele of rs2228570 in VDR, as well as heterozygous genotype of rs4588 in VDBP, were found statistically high in patients. Total cholesterol, triglyceride, and LDL-C levels were found significantly high whereas HDL-C and vitamin D levels were low in patients. An association was found between rs4588 variation and high triglyceride levels. Similar correlations were found between ε2 genotype and low LDL-C level; ε3 genotype and higher LDL-C. Gender, triglyceride, HDL-C, and AA genotype in rs4588 had a significant effect on MS progression. Conclusion The variations of rs2228570 and rs4588, vitamin D deficiency, and biological parameters related to cholesterol metabolism may be associated with MS risk.
... Using graph theory formalism, previous studies found evidence of the ApoE4-related modulation on healthy aging, MCI, and the AD covariance brain network based on physiological variables derived from different image modalities (rsFMRI, FDG-PET, and DWI) (Brown et al., 2011;Giau et al., 2015;Goryawala et al., 2015;Li et al., 2019;Sanabria-Diaz et al., 2021;Seo et al., 2013;Wang et al., 2015;Yao et al., 2015;Zhu et al., 2018). Their findings propose a link between the possession of ApoE4 and brain network organization abnormalities in AD, suggesting disease-related disconnection mechanisms (Delbeuck et al., 2003;Filippi and Agosta, 2011;He et al., 2009). ...
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There is evidence that gray matter networks are disrupted in Mild Cognitive Impairment (MCI) and associated with cognitive impairment and faster disease progression. However, it remains unknown how these alterations are related to the presence of Apolipoprotein E isoform E4 (ApoE4), the most prominent genetic risk factor for late-onset Alzheimer’s disease (AD). To investigate this topic at the individual level, we explore the impact of ApoE4 and the disease progression on the Single-Subject Gray Matter Networks (SSGMNets) using the graph theory approach. Our data sample comprised 200 MCI patients selected from the ADNI database, classified as non-Converters and Converters (will progress into AD). Each group included 50 ApoE4-positive (‘Carriers', ApoE4+) and 50 ApoE4-negative ('non-Carriers', ApoE4-). The SSGMNets were estimated from structural MRIs at two-time points: baseline and conversion. We investigated whether altered network topological measures at baseline and their rate of change (RoC) between baseline and conversion time points were associated with ApoE4 and disease progression. We also explored the correlation of SSGMNets attributes with general cognition score (MMSE), memory (ADNI-MEM), and CSF-derived biomarkers of AD (Aβ42, T-tau, and P-tau). Our results showed that ApoE4 and the disease progression modulated the global topological network properties independently but not in their RoC. MCI converters showed a lower clustering index in several regions associated with neurodegeneration in AD. The SSGMNets' topological organization was revealed to be able to predict cognitive and memory measures. The findings presented here suggest that SSGMNets could indeed be used to identify MCI ApoE4 Carriers with a high risk for AD progression.
... Plasma Aβ levels were detected using ELISA, which has been demonstrated as an accurate and dependable method (Katzman et al., 1988). We did a multiple analysis to adjusted for almost all identified potential confounder factors, including the ApoE genotype (Rodrigue et al., 2013;Giau et al., 2015), BMI (Qiu et al., 2005), MMSE score, and serum TC, TG and HDL-c levels (Matsuzaki et al., 2011). The relationships between plasma Aβ level and BP levels did not change. ...
... The underlying mechanism is not clear. As the strongest genetic risk factor for AD, the ApoE ε4 allele was closely associated with the decrease of cerebral spinal flow Aβ and the increase of aggregation and deposition of cerebral Aβ in the brain (Liu et al., 2013;Giau et al., 2015). ApoE ε4 might compromise the effects of BP on plasma Aβ levels. ...
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Objectives : Amyloid-β (Aβ) deposition in the brain is the hallmark of Alzheimer’s disease (AD) pathology. Hypertension is a risk factor for AD, but the effects of hypertension on Aβ deposition are not fully determined. Considering peripheral Aβ closely relates to Aβ deposition in the brain, we investigated the relationships between blood pressure (BP) level and plasma Aβ concentrations. Methods : One-thousand and sixty-nine participants (age above 45) from a village in the suburbs of Xi’an, China were enrolled. Questionnaires and validated Chinese versions of the Mini-Mental State Examination (MMSE) were used to collect information about vascular risk factors and assess cognition function. The apolipoprotein E (ApoE) genotype was detected using PCR and sequencing. Plasma Aβ levels were measured using ELISA. The associations between BP and plasma Aβ levels were analyzed by using multivariate linear regression. Results : Plasma Aβ 1–40 level was higher in high BP group than that in normal BP group (53.34 ± 8.50 pg/ml vs. 51.98 ± 8.96 pg/ml, P = 0.013), in high SBP group than that in normal SBP group (53.68 ± 8.69 pg/ml vs. 51.88 ± 8.80 pg/ml, P = 0.001) and in high MABP group than that in normal MABP group (54.05 ± 8.78 pg/ml vs. 52.04 ± 8.75 pg/ml, P = 0.001). After controlling for the confounding factors, SBP ( b = 0.078, P < 0.001), DBP ( b = 0.090, P = 0.008) and MABP ( b = 0.104, P < 0.001) correlated with plasma Aβ 1–40 level positively in ApoE ε4 non-carriers, but not ApoE ε4 carriers. Conclusions : Elevated BP levels were associated with increased plasma Aβ 1–40 levels in middle-aged and elderly ApoE ε4 non-carriers.