Apo D and Apo E Levels in Autism Spectrum Disorders

Apo D is an atypical plasma apolipoprotein and a member of the lipocalin protein superfamily. In recent years, Apo D has been identified as an important factor in the pathology of neurodegenerative and neuropsychiatric diseases. Apo D is highly produced in the brain and acts as a multiligand and multifunctional carrier. Apo D binds to and stabilizes Arachidonic acid in the cell membrane and cytosol. Thus, it suppresses inflammation and protects the cell membrane against oxidation. Apo E is important in cholesterol transfer and it has been reported that it may play a role in immune regulation, nerve regeneration, synaptogenesis and neuronal homeostasis. In this study, plasma Apo D and Apo E levels were examined and its possible role in Autism Spectrum Disorders (ASD) pathology was investigated. Thirty-nine subjects with ASD were compared with 30 healthy subjects who typically developed. Accordingly, plasma Apo D and Apo E levels were statistically significantly lower in the ASD group compared to the healthy control group. According to the results of this study, it can be suggested that low levels of Apo D and Apo E may play a role in ASD pathogenesis.

Investigating Effects of Plasma Apolipoprotein E on Ischemic Heart Disease Using Mendelian Randomization Study

Background: Observationally plasma apolipoprotein E (apoE) is positively associated with ischemic heart disease (IHD). A Mendelian randomization (MR) study suggesting apoE is unrelated to cardiovascular mortality did not consider specific isoforms. We used MR to obtain estimates of plasma apoE2, apoE3 and apoE4 on IHD, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides and apolipoprotein B (apoB). Methods: We obtained independent genetic instruments from proteome genome-wide association studies (GWAS) and applied them to large outcome GWAS. We used univariable MR to assess the role of each isoform and multivariable MR to assess direct effects. Results: In univariable MR, apoE4 was positively associated with IHD (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01 to 1.09), but apoE2 and apoE3 were less clearly associated. Using multivariable MR an association of apoE2 with IHD (OR 1.16, 95% CI 0.98 to 1.38) could not be excluded, and associations of apoE3 and apoE4 with IHD were not obvious. In univariable MR, apoE2 and apoE4 were positively associated with apoB, and a positive association of apoE2 with LDL cholesterol could not be excluded. Using multivariable MR apoE2 was positively associated with LDL cholesterol, and associations with apoB could not be excluded. After adjusting for apoB, no direct effects of apoE isoforms on IHD were evident. Conclusions: Plasma apoE2 and apoE4 may play a role in lipid modulation and IHD. Whether apoE could be a potential therapeutic target requires further clarification when larger genetic studies of apoE isoforms are available.

Relationship Between Hyperuricemia and Apolipoprotein AI in Chinese Healthy People: a Cohort Study

Background: Hyperuricemia is an independent risk factor for various cardiovascular diseases. However the association of plasma uric acid and Apolipoprotein AI among Chinese healthy people is still unclear.Aims: To evaluate the relationship between blood uric acid and Apolipoprotein AI level in Chinese healthy people. Method; A total of 3501 normal healthy subjects who were undergone physical examination were divided into hyperuricemia (HUA) group and normouricemia (NUA) group.Result: Apo AI (1.33±0.21 vs. 1.47±0.26) and HDL-c (1.12±0.27 vs. 1.36±0.33)decreased significantly in HUA group than NUA group. LDL-C(2.81±0.77 vs. 2.69±0.73),Apo B(0.96±0.20 vs. 0.89±0.20), FBG(5.48±0.48 vs. 5.36±0.48) and HOMA-IR(2.75（1.92-3.91）vs. 2.18（1.50-3.12）) was significantly higher in HAU group than NUA group. Increased plasma UA was correlated with decreased HDL-c(r=-0.289, P<0.01 ) and Apo AI(r=-0.236, p<0.01) .Conclusion: Hyperuricemia was associated with decreased plasma Apolipoprotein AI and HDL-c. Inhibiting Apolipoprotein AI may be one of the mechanisms of UA involved in the progression of cardiovascular disease.

Plasma Apolipoprotein E3 and Glucose Levels Are Associated in APOE ɛ3/ɛ4 Carriers

Background: Altered cerebral glucose metabolism, especially prominent in APOE ɛ4 carriers, occurs years prior to symptoms in Alzheimer’s disease (AD). We recently found an association between a higher ratio of plasma apolipoprotein E4 (apoE4) over apoE3, and cerebral glucose hypometabolism in cognitively healthy APOE ɛ3/ɛ4 subjects. Plasma apoE does not cross the blood-brain barrier, hence we speculate that apoE is linked to peripheral glucose metabolism which is known to affect glucose metabolism in the brain. Objective: Explore potential associations between levels of plasma insulin and glucose with previously acquired plasma apoE, cerebral metabolic rate of glucose (CMRgl), gray matter volume, and neuropsychological test scores. Methods: Plasma insulin and glucose levels were determined by ELISA and a glucose oxidase assay whereas apoE levels were earlier quantified by mass-spectrometry in 128 cognitively healthy APOE ɛ3/ɛ4 subjects. Twenty-five study subjects had previously undergone FDG-PET and structural MRI. Results: Lower plasma apoE3 associated with higher plasma glucose but not insulin in male subjects and subjects with a body mass index above 25. Negative correlations were found between plasma glucose and CMRgl in the left prefrontal and bilateral occipital regions. These associations may have functional implications since glucose levels in turn were negatively associated with neuropsychological test scores. Conclusion: Plasma apoE3 but not apoE4 may be involved in insulin-independent processes governing plasma glucose levels. Higher plasma glucose, which negatively affects brain glucose metabolism, was associated with lower plasma apoE levels in APOE ɛ3/ɛ4 subjects. High plasma glucose and low apoE levels may be a hazardous combination leading to an increased risk of AD.

Elevated apolipoprotein A1 and HDL cholesterol associated with age-related macular degeneration: two population cohorts

Context To enable prevention and treatment of age-related macular degeneration(AMD), understanding risk factors for AMD is important. Objective We tested the hypotheses that elevated plasma apolipoprotein A1 and high-density lipoprotein(HDL) cholesterol, and low levels of low-density lipoprotein(LDL) cholesterol, are associated with increased risk of AMD. Design and Setting From the Danish general population, we studied 106,703 and 16,032 individuals in the Copenhagen General Population Study(CGPS) and the Copenhagen City Heart Study(CCHS) with median follow-up of respectively 9 and 32 years. Main Outcome Measures 1,787 AMD in CGPS and 206 in CCHS. Results Higher concentrations of plasma apolipoprotein A1 and HDL cholesterol, and lower concentrations of LDL cholesterol, were associated with higher risk of AMD in CGPS. After multifactorial adjustment, individuals in the highest versus lowest quartile of plasma apolipoprotein A1 and HDL cholesterol had hazard ratios for AMD of 1.40(95%CI:1.20-1.63) and 1.22(1.03-1.45). Corresponding hazard ratios for individuals in the lowest versus highest quartile of LDL cholesterol were 1.18(1.02-1.37). Per 100 mg/dL higher plasma apolipoprotein A1, 1 mmol/L(39 mg/dL) higher HDL, and 1 mmol/L(39mmol/L) lower LDL cholesterol, the hazard ratios for AMD were 1.53(1.31-1.80), 1.19(1.07-1.32), and 1.05(1.00-1.11), respectively, with similar results across strata of different risk factors. Higher concentrations of HDL cholesterol were also associated with higher risk of AMD in the CCHS. Conclusion Elevated plasma apolipoprotein A1 and HDL cholesterol, and lower LDL cholesterol, are associated with increased risk of age-related macular degeneration.

Hyperlipidemic Rabbit Models for Anti-Atherosclerotic Drug Development

Hyperlipidemia or dyslipidemia is a major risk factor for atherosclerotic diseases. Experimental animals play an important role in elucidating the molecular mechanisms of the pathophysiology of hyperlipidemia as well as in drug development. Rabbits are one of the most suitable models to study human hyperlipidemia because many features of the lipoprotein metabolism of rabbits are similar to those of humans such as LDL-rich lipoproteins in plasma, apolipoprotein B mRNA editing, and cholesteryl ester transfer protein. Currently, three types of rabbit models are commonly used for studying hyperlipidemia: (1) diet-induced hyperlipidemic rabbits, (2) spontaneous hyperlipidemic rabbits, and (3) gene-manipulated rabbits (transgenic and knockout rabbits). In this review, we give an overview of the features of hyperlipidemic rabbits and discuss the usefulness of rabbits for the development of anti-atherogenic drugs.

An Exploratory Analysis of Changes in Mental Wellbeing Following Curcumin and Fish Oil Supplementation in Middle-Aged and Older Adults

Curcumin has previously been shown to enhance mood in non-depressed older adults. However, observed benefits were limited to short-term supplementation (4 weeks). In a 16 week randomized, double-blind, placebo-controlled, 2 × 2 factorial design trial, we supplemented overweight or obese non-depressed adults (50–80 years) with curcumin (160 mg/day), fish oil (2000 mg docosahexaenoic acid +400 mg eicosapentaenoic acid/day), or a combination of both. Secondary outcomes included mental wellbeing measures (mood states and subjective memory complaints (SMCs)) and quality of life (QoL). Furthermore, plasma apolipoprotein E4 (APOE4) was measured to determine whether APOE4 status influences responses to fish oil. Curcumin improved vigour (p = 0.044) compared to placebo and reduced SMCs compared to no curcumin treatment (p = 0.038). Fish oil did not affect any mood states, SMCs or QoL; however, responses to fish oil were affected by APOE4 status. In APOE4 non-carriers, fish oil increased vigour (p = 0.030) and reduced total mood disturbances (p = 0.048) compared to placebo. Improvements in mental wellbeing were correlated with increased QoL. Combining curcumin with fish oil did not result in additive effects. This exploratory analysis indicates that regular supplementation with either curcumin or fish oil (limited to APOE4 non-carriers) has the potential to improve some aspects of mental wellbeing in association with better QoL.