Levels Of Apolipoprotein Research Articles

Serum metabolomic profiling correlated with ISS and clinical outcome for multiple myeloma patients treated with high-dose melphalan and autologous stem cell transplantation

The metabolome, which is the final down-stream global product of metabolic processes in organisms, is not sufficiently described in multiple myeloma (MM) patients. The aim of this study was, therefore, to study the serum metabolomic profile using proton nuclear magnetic resonance (1H-NMR) spectroscopy, and its relationship to clinical characteristics and patient outcome. Serum samples, which were taken at diagnosis, from 201 MM patients who underwent high-dose melphalan followed by autologous stem cell transplantation as the first-line therapy, were analyzed. We found that the metabolomic profile differed between patients with different MM International Staging System (ISS) stages. The profile revealed increased levels of cholesterol, phospholipids, high-density lipoprotein, low-density lipoprotein, apolipoproteins A1 and A2, valine, and leucine in ISS I patients compared with ISS III patients. The metabolomic profile also differed between patients with IgA and IgG paraproteins, predominantly because of higher levels of high- and low-density lipoprotein subfractions in IgA patients. The exact pathway of metabolism leading to accumulation of these metabolites is still elusive, but this study indicates an area of interest for further investigation in the search for new therapy targets and prognostic markers for this disease.

The association of parameters of body composition and laboratory markers with the severity of hypertriglyceridemia-induced pancreatitis

BackgroundHypertriglyceridemia has arisen as the third leading cause of acute pancreatitis. This study aimed at exploring the association between the severity of hypertriglyceridemia-induced pancreatitis (HTGP) and computed tomography (CT)-based body composition parameters and laboratory markers.MethodsLaboratory and clinical parameters were collected from 242 patients with HTGP between 2017 and 2020. Severity of HTGP was evaluated by original or modified CT severity index. Body composition parameters such as area and radiodensity of muscle, subcutaneous adipose tissue and visceral adipose tissue were calculated by CT at the level of third lumbar vertebra. Parameters were compared between mild and moderately severe to severe HTGP. Uni-variate and multi-variate Logistic regression analyses were employed to assess the risk factors of the severity of HTGP.ResultsSeventy patients (28.9%) presented with mild HTGP. Body mass index, waist circumference and all CT-based body composition parameters differed between male and female patients. None was associated with the severity of HTGP, neither in males nor in females. Receiver operating characteristic curves showed that areas under the curves of apolipoprotein A-I and albumin to predict the severity of HTGP were 0.786 and 0.759, respectively (all P < 0.001). Uni-variate and further multi-variate Logistic regression analysis confirmed that low serum albumin (< 35 g/L, P = 0.004, OR = 3.362, 95%CI = 1.492–8.823) and apolipoprotein A-I (< 1.1 g/L, P < 0.001, OR = 5.126, 95%CI = 2.348–11.195), as well as high C-reactive protein (> 90 mg/L, P = 0.005, OR = 3.061, 95%CI = 1.407–6.659) and lipase (P = 0.033, OR = 2.283, 95%CI = 1.070–4.873) were risk factors of moderately severe to severe HTGP. Levels of albumin, apolipoprotein A-I, C-reactive protein and lipase were also associated with the length of hospital stay (all P < 0.05). Besides, low serum albumin, low-density lipoprotein cholesterol and high radiodensity of subcutaneous adipose tissue were significant risk factors of pancreatic necrosis in patients with HTGP (all P < 0.05).ConclusionsLow serum albumin and apolipoprotein A-I, and high C-reactive protein and lipase upon admission were associated with a more severe type of HTGP and longer hospital stay for these patients. Albumin and apolipoprotein A-I may serve as novel biomarkers for the severity of HTGP. However, none of the body composition parameters was associated with the severity of HTGP.

Association Between Serum Lipid Levels and Patients With Primary Angle-Closure Glaucoma in China: A Cross Sectional, Case–Control Study

Objective: To evaluate the serum lipid levels of patients with primary angle-closure glaucoma (PACG) and to investigate the relationship between serum lipid levels and PACG.Methods: In this cross-sectional, case–control study, a total of 320 PACG subjects and 242 age- and sex-matched control subjects were recruited. Serum high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (SDLDL-C), triglyceride (TRIG), and cholesterol (CHOL) levels were measured using enzymatic colorimetry. Serum apolipoprotein A (APOA), apolipoprotein B (APOB), apolipoprotein E (APOE), and lipoprotein(a) (LPa) levels were measured by immunoturbidimetry.Results: The serum LDL-C, TRIG, HDL-C, APOE, LPa, CHOL, APOB, and APOA levels were significantly higher (p < 0.05) in the PACG group than in the control group. Multiple liner regression analyses revealed that there was a statistically correlation between HDL-C levels and mean deviation MD (B = 0.389, P = 0.002, 95% confidence interval [CI] = −1.249 to −0.624); LDL-C levels and MD (B = 0.190, P = 0.019, 95% CI = −5.632 to −1.306); and CHOL levels and MD (B = 0.364, P = 0.27, 95% CI = −7.727 to −1.839). Logistic regression analyses showed that high serum HDL-C (odds ratio [OR] = 11.01, 95% CI = 5.616–21.587), LDL-C (OR = 1.330, 95% CI = 1.079–1.640), SDLDL-C (OR = 1.007, 95% CI = 1.005–1.008), APOA (OR = 13.621, 95% CI = 7.251–25.591), APOB (OR = 2.243, 95% CI = 1.060–4.732), LPa (OR = 0.999, 95% CI = 0.998–1.00), and CHOL (OR = 1.131, 95% CI = 1.005–1.326) levels were significantly associated with PACG.Conclusions: High serum HDL-C, LDL-C, APOA, APOB, LPa, and CHOL levels were associated with PACG.

Dietary lipid levels affected growth performance, lipid accumulation, inflammatory response and apoptosis of japanese seabass (lateolabraxjaponicus)

An eight weeks feeding trial was conducted to investigate the effects of dietary lipid levels on growth performance, lipid metabolism and immune response of Japanese seabass (Lateolabrax japonicus). Five diets were formulated with gradient dietary lipid levels (79.6, 104.4, 129.1, 154.9 and 178.6 g kg−1). Results revealed that growth and feed utilization of fish were significantly lower in group L178.6 than other groups (p < 0.05). Lipid accumulation in whole body, muscle and intraperitoneal were increased with increasing dietary lipid levels. The mRNA levels of adipose triglyceride lipase, carnitine palmitoyl transferase 1, acetyl CoA carboxylase, cholesterol 7 alpha-hydroxylase and retinoid X receptor in liver were also increased with increasing dietary lipid levels (p < 0.05). The mRNA levels of apolipoprotein A1 and peroxisome proliferator activating receptor α were higher in fish fed L178.6 than those fed other diets. Oxidative stress in plasma and liver were induced when dietary lipid exceed 154.9 g kg−1. L154.9 and L178.6 significantly increased the inflammatory related gene expression of fish. These results suggested that high-fat diet impaired the growth performance and induced lipid accumulation, inflammation and apoptosis of Japanese seabass. The suitable dietary lipid level of Japanese seabass may not exceed 129.1 g kg−1.

Glucocorticoid signaling and lipid metabolism disturbances in the liver of rats treated with 5α-dihydrotestosterone in an animal model of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complex reproductive disorder often associated with obesity, insulin resistance, and dyslipidemia. Hormonal changes in PCOS may also include altered glucocorticoid signaling. Our aim was to examine whether alterations in hepatic glucocorticoid signaling are associated with disturbances of glucose and lipid metabolism in animal model of PCOS. Female rats, 3 weeks old, were subcutaneously implanted with 5α-dihydrotestosterone (DHT) or placebo pellets for 90 days to induce PCOS. Expression of 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) and A-ring reductases (5α and 5β), as well as intracellular distribution of glucocorticoid receptor (GR) and expression of its regulated genes were examined in the liver. Proteins of hepatic lipid and carbohydrate metabolism and markers of inflammation were also assessed. DHT treatment induced increase in body and liver mass, as well as in triglycerides and free fatty acids levels in plasma. Elevation of 11βHSD1 and reduction of 5α-reductase expression was observed together with increased hepatic corticosterone concentration and nuclear GR activation. Induced expression of Krüppel-like factor 15 and decreased expression of genes for proinflammatory cytokines and de novo lipogenesis (DNL) were detected in the liver of DHT-treated rats, while DNL regulators and proinflammatory markers were not changed. However, increased mRNA levels of stearoyl-CoA desaturase and apolipoprotein B were observed in DHT animals. DHT treatment stimulated hepatic glucocorticoid prereceptor metabolism through increased corticosterone availability which is associated with enhanced GR activation. This does not affect gluconeogenesis and DNL, but could be linked to stimulated triglyceride synthesis and hypertriglyceridemia.

Comparison of Plasma Lipoprotein Composition and Function in Cerebral Amyloid Angiopathy and Alzheimer's Disease.

Cerebral amyloid angiopathy (CAA) refers to beta-amyloid (Aβ) deposition in brain vessels and is clinically the main cause of lobar intracerebral hemorrhage (ICH). Aβ can also accumulate in brain parenchyma forming neuritic plaques in Alzheimer’s disease (AD). Our study aimed to determine whether the peripheral lipid profile and lipoprotein composition are associated with cerebral beta-amyloidosis pathology and may reflect biological differences in AD and CAA. For this purpose, lipid and apolipoproteins levels were analyzed in plasma from 51 ICH-CAA patients (collected during the chronic phase of the disease), 60 AD patients, and 60 control subjects. Lipoproteins (VLDL, LDL, and HDL) were isolated and their composition and pro/antioxidant ability were determined. We observed that alterations in the lipid profile and lipoprotein composition were remarkable in the ICH-CAA group compared to control subjects, whereas the AD group presented no specific alterations compared with controls. ICH-CAA patients presented an atheroprotective profile, which consisted of lower total and LDL cholesterol levels. Plasma from chronic ICH-CAA patients also showed a redistribution of ApoC-III from HDL to VLDL and a higher ApoE/ApoC-III ratio in HDL. Whether these alterations reflect a protective response or have a causative effect on the pathology requires further investigation.

Association of serum HDL-cholesterol and apolipoprotein A1 levels with risk of severe SARS-CoV-2 infection

Individuals with features of metabolic syndrome are particularly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus associated with the severe respiratory disease, coronavirus disease 2019 (COVID-19). Despite considerable attention dedicated to COVID-19, the link between metabolic syndrome and SARS-CoV-2 infection remains unclear. Using data from the UK Biobank, we investigated the relationship between severity of COVID-19 and metabolic syndrome-related serum biomarkers measured prior to SARS-CoV-2 infection. Logistic regression analyses were used to test biomarker levels and biomarker-associated genetic variants with SARS-CoV-2-related outcomes. Among SARS-CoV-2-positive cases and negative controls, a 10 mg/dl increase in serum HDL-cholesterol or apolipoprotein A1 levels was associated with ∼10% reduced risk of SARS-CoV-2 infection, after adjustment for age, sex, obesity, hypertension, type 2 diabetes, and coronary artery disease. Evaluation of known genetic variants for HDL-cholesterol revealed that individuals homozygous for apolipoprotein E4 alleles had ∼2- to 3-fold higher risk of SARS-CoV-2 infection or mortality from COVID-19 compared with apolipoprotein E3 homozygotes, even after adjustment for HDL-cholesterol levels. However, cumulative effects of all evaluated HDL-cholesterol-raising alleles and Mendelian randomization analyses did not reveal association of genetically higher HDL-cholesterol levels with decreased risk of SARS-CoV-2 infection. These results implicate serum HDL-cholesterol and apolipoprotein A1 levels measured prior to SAR-CoV-2 exposure as clinical risk factors for severe COVID-19 infection but do not provide evidence that genetically elevated HDL-cholesterol levels are associated with SAR-CoV-2 infection.

Effect of APOE ε4 allele on levels of apolipoproteins E, J, and D, and redox signature in circulating extracellular vesicles from cognitively impaired with no dementia participants converted to Alzheimer's disease.

IntroductionThe substantial link between apolipoprotein E (APOE) ε4 allele and oxidative stress may underlie enhanced Alzheimer's disease (AD) risk. Here, we studied the impact of APOE ε4 on the level of apolipoproteins with antioxidant activities along with oxidative markers in circulating extracellular vesicles (cEVs) and plasma from cognitively impaired‐not demented (CIND) individuals converted to AD (CIND‐AD).MethodsApolipoproteins E, J, and D and antioxidant response markers were determined in cEVs and plasma using immunoblotting, electrochemical examination, and spectrofluorimetry.ResultsTotal antioxidant capacity and apolipoprotein D levels in cEVs, as judged by regression analysis and cognitive performance correlations, allowed us to differentiate CIND APOE ε4 carriers from controls and to predict their progression to AD 5 years later.DiscussionOur findings support the pathological redox linkage between APOE ε4 and AD onset and suggest the use of cEVs oxidative signature in early AD diagnosis.

Apolipoprotein A1 and Low-Density Lipoprotein as Risk Factors for Intraocular Metastases in Postmenopausal Breast Cancer.

Background:The outcomes of patients with postmenopausal breast cancer(PBC) can be improved through the early detection of intraocular metastases(IOMs). In this study, we investigated patients with PBC, and compared those with IOMs with those with non-intraocular metastases(NIOMs) in terms of blood lipid levels, and then differentiated the risk factors associated with IOMs.Methods:Student’s t-test and a chi-square test were used to discriminate between the IOMs and NIOMs groups. After establishing a Poisson regression model to analyze risk factors, we plotted receiver operating characteristic curves(ROC) to assess the quality of risk factors predicting IOMs.Results:The incidence of IOMs in PBC was 1.16%. There was no significant difference in terms of histopathology between the 2 groups. The levels of total cholesterol (TC), apolipoprotein A1(APOA1) and low-density lipoprotein(LDL) in IOMs were significantly lower than in NIOMs groups. Poisson regression suggested that low levels of APOA1 and LDL were risk factors for IOMs (P = 0.002 and P < 0.001, respectively). ROC curve analysis demonstrated that the cut-off values of APOA1 and LDL were 1.025 g/L and 2.415 mmol/L. The highest prediction accuracy for IOMs involved the combination of APOA1 and LDL (AUC = 0.881, P < 0.001).Conclusion:Our research demonstrates that low levels of APOA1 and LDL efficiently predict IOMs in PBC as risk factors, and the combination of APOA1 and LDL was more predictive than single factors.

Atherosclerosis-associated hepatic secretion of VLDL but not PCSK9 is dependent on cargo receptor protein Surf4

Plasma LDL is produced from catabolism of VLDL and cleared from circulation mainly via the hepatic LDL receptor (LDLR). Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes LDLR degradation, increasing plasma LDL-C levels. Circulating PCSK9 is mainly secreted by the liver, whereas VLDL is exclusively secreted by hepatocytes. However, the mechanism regulating their secretion is not completely understood. Surfeit 4 (Surf4) is a cargo receptor localized in the ER membrane. It recruits cargos into coat protein complex II vesicles to facilitate their secretion. Here, we investigated the role of Surf4 in VLDL and PCSK9 secretion. We generated Surf4 liver-specific knockout mice and found that knockout of Surf4 did not affect PCSK9 secretion, whereas it significantly reduced plasma levels of cholesterol, triglyceride, and lipid-binding protein apolipoprotein B (apoB). In cultured human hepatocytes, Surf4 coimmunoprecipitated and colocalized with apolipoprotein B100, and Surf4 silencing reduced secretion of apolipoprotein B100. Furthermore, knockdown of Surf4 in LDLR knockout (Ldlr−/−) mice significantly reduced triglyceride secretion, plasma levels of apoB and non-HDL-C, and the development of atherosclerosis. However, Surf4 liver-specific knockout mice and Surf4 knockdown in Ldlr−/− mice displayed similar levels of liver lipids and plasma alanine aminotransferase activity as control mice, indicating that inhibition of Surf4 does not cause notable liver damage. Expression of stearoyl-CoA desaturase-1 was also reduced in the liver of these mice, suggesting a reduction in de novo lipogenesis. In summary, hepatic deficiency of Surf4 reduced VLDL secretion and the development of atherosclerosis but did not cause significant hepatic lipid accumulation or liver damage.

Stability of serum biochemical markers during standard long-term storage and with a single thawing

Aim. To study the effect of standard serum long-term storage at -70О C and with a single thawing on the biochemical markers by comparing the results of studies carried out in 2013-2014 and 2020.Material and methods. The material was the blood serum of participants in the ESSE-RF study, which was stored in a specialized biobank from 2013-2014 at -70О C either continuously (n=149) or with a single thawing (n=20). Initially and in 2020, the quantitative determination of serum biochemical parameters was carried out using same equipment and standard techniques.Results. Long-term storage at -70О C led to mild, but significant changes in almost all analyzed parameters: low density lipoprotein cholesterol (LDL-C) and apolipoprotein A1 levels decreased; levels of highdensity lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein B, glucose, and high-sensitivity C-reactive protein increased. Insulin and thyroid-stimulating hormone levels did not change during storage. The revealed strong positive relationships between the initial concentrations and those measured in 2020 in samples that were stored continuously indicate the relevance of such storage. In samples with single thawing, changes in most parameters were more pronounced.Conclusion. The results of a prospective cohort study aimed at studying the stability of human serum samples during storage indicate the validity of long-term storage at -70О C without thawing. Freeze-thawing cycle of samples (even once) is unacceptable, since it leads to a pronounced LDL-C decrease. Given the fact that it is the LDL-C levels that is the target of lipid-lowering therapy, continuous low-temperature (not &gt;-70О C) storage of blood serum samples is recommended.

Study on the association between serum APO-E levels and serum lipid levels in young smokers

Smoking causes cardiovascular deaths which are about11% of total global death. Cigarette smoking is one of the significant risk factors for cardiovascular disease and atherosclerosis in young age. Apo lipoprotein-E (APO-E) is a glycoprotein which plays an important role in lipid metabolism. However, the relation between serum APO-E levels and serum lipid levels remains controversial. So we aim to find out the association between serum APO-E levels and serum lipid levels in young smokers. The study contains 60 young smokers with CHD aged between 20 to 45 years, and 60 healthy normal individuals were attending in Cardiology OP, Medicine OP and MHC were selected for the study. Serum APO-E levels were measured by Enzyme-linked Immune Sorbent Assay (ELISA), and the lipid profile was measured by the enzymatic method. The mean serum APO-E levels were significantly (p-value &lt;0.0001) higher in smokers with CHD when compared to the controls. A positive correlation was found between the serum APO-E level and BMI (r-value=0.595), FBG (r-value=0.425), TC (r-value=0.650), TGL (r-value=0.449), LDL (r-value=0.456 ), VLDL (r-value=0.452 ), No of smoking/day (r-value=0.862 ), duration of smoking (r-value=0.726 ) and a negative correlation was found with HDL-C levels. The current study gives a significant correlation between smoking and lipid profile in young smokers. Thus the present study concludes that cigarette smoking produced a significant effect on serum APO-E levels and lipid profile in young smokers which may lead to cardiovascular disease in young smokers.

A study on lipid profile and apolipoprotein levels in psoriatic patients

Background: Psoriasis is a chronic, recurrent, inflammatory, and proliferative disease. Previous studies have demonstrated that patients with psoriasis may have an increased risk of developingcoronary artery disease. High serum lipid levels have been suggested in the pathogenesis of this phenomenon. Accumulating evidence suggests that apolipoprotein B is superior to other lipidparameters in predicting atherosclerotic cardiovascular disease. This study aimed to examine the differences in the lipid profile and apolipoprotein A-I and apolipoprotein B levels between psoriatic patients and healthy subjects.Methods: This was a case-control, cross-sectional study. A total of 93 psoriatic patients and 113 healthy individuals were enrolled. This study was conducted at the outpatient department of dermatology in Alsader Teaching Hospital, Basra, Iraq. The serum level of total cholesterol (TC), triglyceride (TG), very lowdensity lipoprotein cholesterol (VLDL-C), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I and apolipoprotein B were measured.Results: The psoriatic patients had significantly higher levels of TC, TG, VLDL-C, LDL-C, and apolipoprotein B compared with the control group.Conclusion: Lipid profile values were significantly higher among patients with psoriasis than normal controls. Early screening and treatment of hyperlipidemia in these patients are advisable toprevent atherosclerosis and its complications. Apolipoprotein B may serve as a marker for dyslipidemia and CVD in patients with psoriasis.

Role of Lipids and Apolipoproteins in Predicting the Prognosis of Hepatocellular Carcinoma After Resection.

PurposeTo further clarify the association between abnormal levels of serum lipid components as the main features of dyslipidaemia and hepatocellular carcinoma, which remains unclear.Patients and MethodsWe examined the serum level of lipids and apolipoproteins pattern in 471 patients undergoing curative resection for HCC, 193 patients with chronic liver disease, and 104 patients with benign liver diseases. We performed uni- and multivariate analyses to evaluate the predictive roles of lipids and apolipoproteins for recurrence and survival of HCC in a training cohort of 242 patients and then validated in a cohort of 229 patients.ResultsThe majority circulating lipid and apolipoprotein levels such as ApoA1, HDL, and LDL in chronic liver disease and HCC were slightly significantly decreased as compared to those in benign lesion. But no significant differential expression patterns of lipids and apolipoproteins were observed between chronic liver hepatitis and HCC. Multivariable analysis identified ApoA1 as a key parameter related to recurrence and survival in both training and validation cohorts. Moreover, we further demonstrated that low ApoA1 was an independent prognostic factor of poor early recurrence in two cohorts.ConclusionAlthough the alterations of circulating lipids and apolipoproteins were observed in HCC, none of lipids or apolipoproteins could serve as a diagnostic marker. Serum ApoA1 merits consideration as a novel prognostic marker for patients with HCC undergoing surgery since it predicts early recurrence and survival, especially for early stage patients and may improve the prognostic stratification of patients for clinical management and promote HCC clinic outcomes.

New Classification and Management of Abetalipoproteinemia and Related Disorders

New Classification and Management of Abetalipoproteinemia and Related Disorders

Apolipoproteins A1 and B and their ratio in acute ischemic stroke patients with intracranial and extracranial arterial stenosis: an Egyptian study

BackgroundApolipoprotein A1 and B and their ratio are considered a better biomarker for cardiovascular diseases than a lipid profile, but this previous finding is not proved to cerebrovascular ischemic diseases. The aim of this study is to assess the relation between apolipoprotien A1 and B and their ratio to intra- and extracranial carotid atherosclerosis in patients with ischemic acute stroke.Methods90 Egyptian patients with acute ischemic stroke are included in the study, and they have been classified into 3 groups: group 1 includes 30 patients with intracranial stenosis, group 2 includes 30 patients with extracranial arterial stenosis, and group 3 includes 30 patients with non-arterial stenosis. Patients were subjected to clinical assessment, routine laboratory measures, and Color-Coded Duplex Sonography for extracranial and intracranial arteries. The measurement of serum levels of apolipoproteins A1 and B was done using enzyme-linked immuno-sorbent assay (ELISA).ResultsA statistically significant difference was found between patient groups as regards the frequency of abnormal serum LDL-cholesterol (p = 0.04), being elevated in patients with extracranial stenosis (p = 0.01). There was a significant difference between patients groups as regards the frequency of abnormal serum HDL-cholesterol (p = 0.02), being lower in patients with extracranial stenosis. High Apo B/A1 ratio was an independent risk factor for intracranial arterial stenosis (p = 0.045). An abnormal elevation of serum LDL cholesterol was an independent risk factor of extracranial arterial stenosis (p = 0.021).ConclusionApo B/A1 ratio is an independent risk factor for intracranial arterial stenosis, while serum LDL cholesterol is an independent risk factor for extracranial arterial stenosis. Apo B/A1 ratio and serum LDL cholesterol are reliable serum biomarkers for cranial arterial stenosis in acute ischemic stroke patients.

An Increased Plasma Level of ApoCIII-Rich Electronegative High-Density Lipoprotein May Contribute to Cognitive Impairment in Alzheimer's Disease.

High-density lipoprotein (HDL) plays a vital role in lipid metabolism and anti-inflammatory activities; a dysfunctional HDL impairs cholesterol efflux pathways. To understand HDL’s role in patients with Alzheimer’s disease (AD), we analyzed the chemical properties and function. HDL from AD patients (AD-HDL) was separated into five subfractions, H1–H5, using fast-protein liquid chromatography equipped with an anion-exchange column. Subfraction H5, defined as the most electronegative HDL, was increased 5.5-fold in AD-HDL (23.48 ± 17.83%) in comparison with the control HDL (4.24 ± 3.22%). By liquid chromatography mass spectrometry (LC/MSE), AD-HDL showed that the level of apolipoprotein (apo)CIII was elevated but sphingosine-1-phosphate (S1P)-associated apoM and anti-oxidative paraoxonase 1 (PON1) were reduced. AD-HDL showed a lower cholesterol efflux capacity that was associated with the post-translational oxidation of apoAI. Exposure of murine macrophage cell line, RAW 264.7, to AD-HDL induced a vibrant expression of ganglioside GM1 in colocalization with apoCIII on lipid rafts alongside a concomitant increase of tumor necrosis factor-α (TNF-α) detectable in the cultured medium. In conclusion, AD-HDL had a higher proportion of H5, an apoCIII-rich electronegative HDL subfraction. The associated increase in pro-inflammatory (apoCIII, TNF-α) components might favor Amyloid β assembly and neural inflammation. A compromised cholesterol efflux capacity of AD-HDL may also contribute to cognitive impairment.

Performance of serum apolipoprotein-A1 as a sentinel of Covid-19

BackgroundSince 1920, a decrease in serum cholesterol has been identified as a marker of severe pneumonia. We have assessed the performance of serum apolipoprotein-A1, the main transporter of HDL-cholesterol, to identify the early spread of coronavirus disease 2019 (Covid-19) in the general population and its diagnostic performance for the Covid-19.MethodsWe compared the daily mean serum apolipoprotein-A1 during the first 34 weeks of 2020 in a population that is routinely followed for a risk of liver fibrosis risk in the USA (212,297 serum) and in France (20,652 serum) in relation to a local increase in confirmed cases, and in comparison to the same period in 2019 (266,976 and 28,452 serum, respectively). We prospectively assessed the sensitivity of this marker in an observational study of 136 consecutive hospitalized cases and retrospectively evaluated its specificity in 7,481 controls representing the general population.ResultsThe mean serum apolipoprotein-A1 levels in the survey populations began decreasing in January 2020, compared to the same period in 2019. This decrease was highly correlated with the daily increase in confirmed Covid-19 cases in the following 34 weeks, both in France and USA, including the June and mid-July recovery periods in France. Apolipoprotein-A1 at the 1.25 g/L cutoff had a sensitivity of 90.6% (95%CI84.2–95.1) and a specificity of 96.1% (95.7–96.6%) for the diagnosis of Covid-19. The area under the characteristics curve was 0.978 (0.957–0.988), and outperformed haptoglobin and liver function tests. The adjusted risk ratio of apolipoprotein-A1 for survival without transfer to intensive care unit was 5.61 (95%CI 1.02–31.0; P = 0.04).ConclusionApolipoprotein-A1 could be a sentinel of the pandemic in existing routine surveillance of the general population. NCT01927133, CER-2020-14.

Novel Protein Biomarkers of Monoamine Metabolism Defects Correlate with Disease Severity.

Genetic defects of monoamine neurotransmitters are rare neurological diseases amenable to treatment with variable response. They are major causes of early parkinsonism and other spectrum of movement disorders including dopa-responsive dystonia. The objective of this study was to conduct proteomic studies in cerebrospinal fluid (CSF) samples of patients with monoamine defects to detect biomarkers involved in pathophysiology, clinical phenotypes, and treatment response. A total of 90 patients from diverse centers of the International Working Group on Neurotransmitter Related Disorders were included in the study (37 untreated before CSF collection, 48 treated and 5 unknown at the collection time). Clinical and molecular metadata were related to the protein abundances in the CSF. Concentrations of 4 proteins were significantly altered, detected by mass spectrometry, and confirmed by immunoassays. First, decreased levels of apolipoprotein D were found in severe cases of aromatic L-amino acid decarboxylase deficiency. Second, low levels of apolipoprotein H were observed in patients with the severe phenotype of tyrosine hydroxylase deficiency, whereas increased concentrations of oligodendrocyte myelin glycoprotein were found in the same subset of patients with tyrosine hydroxylase deficiency. Third, decreased levels of collagen6A3 were observed in treated patients with tetrahydrobiopterin deficiency. This study with the largest cohort of patients with monoamine defects studied so far reports the proteomic characterization of CSF and identifies 4 novel biomarkers that bring new insights into the consequences of early dopaminergic deprivation in the developing brain. They open new possibilities to understand their role in the pathophysiology of these disorders, and they may serve as potential predictors of disease severity and therapies. © 2020 International Parkinson and Movement Disorder Society.

Is it time to change the goals of lipid management in type 1 diabetes mellitus? Changes in apolipoprotein levels during the first year of type 1 diabetes mellitus. Prospective InLipoDiab1 study.

IntroductionApolipoprotein complement is a critical determinant of lipoprotein function and metabolism. The relation between exogenous insulin and apolipoproteins (apos) in newly diagnosed type 1 diabetes mellitus (T1DM) has not yet been studied extensively. The aim of this study was to prospectively observe the changes in serum apos AI (apo AI) and AII (apo AII) in patients with newly diagnosed T1DM and their association with the daily insulin requirement.Material and methodsThirty-four participants of the InLipoDiab1 study aged 26 (IQR: 22–32) were enrolled in this analysis. Apolipoprotein AI and AII concentrations were assessed at diagnosis and at follow-up after 3 weeks, 6 months, and 1 year of insulin treatment. The daily dose of insulin (DDI) was calculated as the amount of short- and long-acting insulin at discharge from the hospital and at follow-up visits.ResultsThe changes in apo AI concentration were observed after 3 weeks of insulin treatment (p = 0.04), with the largest increase between 3 weeks and 6 months of observation (p < 0.001). Apolipoprotein AII level did not change significantly after 3 weeks, while a significant increase was observed between 3 weeks and 6 months of treatment (p < 0.001). The correlations between DDI and apo concentration were not statistically significant.ConclusionsIn the first year of T1DM, there is a significant increase in apos concentration. Due to the significant deviation of apos concentration from accepted norms, changes in the recommendations of lipid control criteria in T1DM may be considered.