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BioRxiv : the Preprint Server For... Jun 2024The effects of sex, race, and Apolipoprotein E ( ) - Alzheimer's disease (AD) risk factors - on white matter integrity are not well characterized. Diffusion MRI data...
INTRODUCTION
The effects of sex, race, and Apolipoprotein E ( ) - Alzheimer's disease (AD) risk factors - on white matter integrity are not well characterized. Diffusion MRI data from nine well-established longitudinal cohorts of aging were free-water (FW)-corrected and harmonized. This dataset included 4,702 participants (age=73.06 ± 9.75) with 9,671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FA ) were used to assess differences in white matter microstructure by sex, race, and ε4 carrier status. Sex differences in FA in association and projection tracts, racial differences in FA in projection tracts, and ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced. There are prominent differences in white matter microstructure by sex, race, and ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted. Sex, race, and ε4 carrier status relate to white matter microstructural integrity Females generally have lower FA compared to males Non-Hispanic Black adults generally have lower FA than non-Hispanic White adults ε4 carriers tended to have higher FW than non-carriers The authors used PubMed and Google Scholar to review literature that used conventional and free-water (FW)-corrected microstructural metrics to evaluate sex, race, and ε4 differences in white matter microstructure. While studies have previously explored differences by sex and ε4 status, less is known about racial differences and no large-scale FW-corrected analysis has been performed. Sex and race were more associated with FA while ε4 status was associated with FW metrics. Association, projection, limbic, and occipital transcallosal tracts showed the greatest differences. Future studies to determine the biological and social pathways that lead to sex, racial, and ε4 differences are warranted.
CONSENT STATEMENT
All participants provided informed consent in their respective cohort studies.
PubMed: 38915636
DOI: 10.1101/2024.06.10.598357 -
Clinical Kidney Journal Jun 2024
PubMed: 38915437
DOI: 10.1093/ckj/sfae161 -
BMC Cardiovascular Disorders Jun 2024This study investigated the possible relationship between the Apo lipoprotein A1 /high-density lipoprotein cholesterol (ApoA1/HDL-C) ratio and coronary artery disease...
INTRODUCTION
This study investigated the possible relationship between the Apo lipoprotein A1 /high-density lipoprotein cholesterol (ApoA1/HDL-C) ratio and coronary artery disease (CAD) in patients with type 2 diabetes (T2D).
METHODS
This was a matched case-control study of 482 patients with T2D in two groups of CAD and (n = 241) non-CAD (n = 241). The patients were classified into four quartiles according to the ApoA1/HDL-C ratio, and multivariate logistic regression analysis was performed to assess the relationship between ApoA1/HDL-C and CAD. ROC analysis was also conducted.
RESULTS
This study showed that the ApoA1/HDL-C ratio has an independent association with CAD in individuals with T2D. The CAD group exhibited a significantly higher ApoA1/HDL-C ratio than those without CAD (p-value = 0.004). Moreover, the risk of CAD increased significantly across the ApoA1/HDL-C ratio quartiles, with the highest odds in the fourth quartile. The second quartile showed an odds ratio (OR) of 2.03 (p-value = 0.048) compared to the first. Moving to the third quartile, the OR increased to 2.23 (p-value = 0.023). The highest OR was noted in the fourth, reaching 3.41 (p-value = 0.001). Employing a cut-off value of 2.66 and an area under the curve (AUC) of 0.885, the ApoA1/HDL-C ratio predicts CAD among patients with T2D with a sensitivity of 75% and a specificity of 91% (p-value < 0.001).
CONCLUSION
The current study revealed an independent association between ApoA1/HDL-C ratio and CAD in patients with T2D. This ratio can be a promising tool for predicting CAD during the follow-up of patients with T2D, aiding in identifying those at higher risk for CAD.
Topics: Humans; Diabetes Mellitus, Type 2; Apolipoprotein A-I; Coronary Artery Disease; Male; Female; Middle Aged; Cholesterol, HDL; Case-Control Studies; Aged; Biomarkers; Predictive Value of Tests; Risk Assessment; Risk Factors; Prognosis
PubMed: 38914982
DOI: 10.1186/s12872-024-03986-w -
Alzheimer's & Dementia (Amsterdam,... 2024The variability in apolipoprotein E () 4-attributed susceptibility to Alzheimer's disease (AD) across ancestries, sexes, and ages may stem from the modulating effects of...
INTRODUCTION
The variability in apolipoprotein E () 4-attributed susceptibility to Alzheimer's disease (AD) across ancestries, sexes, and ages may stem from the modulating effects of other genetic variants.
METHODS
We examined associations of compound genotypes (CompGs) comprising the 4-encoding rs429358, rs2075650, and rs12721046 polymorphisms with AD in White (7181/16,356 AD-affected/unaffected), Hispanic/Latino (2305/2921), and Black American (547/1753) participants across sexes and ages.
RESULTS
The absence and presence of the rs2075650 and/or rs12721046 minor alleles in the 4-bearing CompGs define lower- and higher-AD-risk profiles, respectively, in White participants. They differentially impact AD risks in men and women of different ancestries, exhibiting an increasing, decreasing, flat, and nonlinear-with lower risks at ages younger than 65/70 years and older than 85 years compared to the ages in between-patterns across ages.
DISCUSSION
The 4-bearing CompGs have a potential to differentiate biological mechanisms of sex-, age-, and ancestry-specific AD risks and serve as AD biomarkers.
HIGHLIGHTS
Younger White women carrying the lower-risk (LR) CompG are at small risk of AD.Black carriers of the LR CompG are at negligible risk of AD at 85 years and older.The higher-risk (HR) CompGs confer high AD risk in Whites and Blacks at 70 to 85 years.AD risk decreases with age for Hispanic/Lation women carrying the HR CompGs.Hispanic/Lation carriers of the LR CompG but not HR CompGs have higher AD risk than Blacks.
PubMed: 38912305
DOI: 10.1002/dad2.12600 -
Cardiovascular Endocrinology &... Sep 2024Bempedoic acid (BA) has shown varied efficacy in managing hyperlipidemia. We conducted the most extensive up-to-date meta-analysis, the first to include recent studies... (Review)
Review
Efficacy and outcomes of bempedoic acid versus placebo in patients with hypercholesterolemia: an updated systematic review and meta-analysis of randomized controlled trials.
INTRODUCTION
Bempedoic acid (BA) has shown varied efficacy in managing hyperlipidemia. We conducted the most extensive up-to-date meta-analysis, the first to include recent studies by Nissen et al., which boast the largest sample size.
METHODS
Literature search was done on Medline, EMBASE, and Cochrane Library. The primary endpoint was a change in low-density lipoprotein-cholesterol (LDL-C) levels, while secondary endpoints encompassed changes in lipid parameters, clinical endpoints, and safety endpoints. The least-square mean (LSM) percent change was utilized for lipid changes, with statistical significance set at < 0.05.
RESULTS
This analysis included 12 randomized control trials with 22,249 participants. BA exhibited a substantial reduction in LDL-C levels [LSM % change, -24.34; 95% confidence interval (CI), -27.80 to -20.88; < 0.0001], total cholesterol levels (LSM % change, -16.62; 95% CI, -21.70 to -11.54; < 0.00001) and high-density lipoprotein-cholesterol (HDL-C) levels (LSM % change, -4.22; 95% CI, -5.51 to -2.92; < 0.00001) compared to the placebo.
CONCLUSIONS
BA significantly lowers LDL-C, total cholesterol, HDL-C, non-HDL-C, high sensitivity C reactive protein, and apolipoprotein levels.
PubMed: 38911912
DOI: 10.1097/XCE.0000000000000302 -
Biomarker Insights 2024Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using...
BACKGROUND
Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using colonoscopy, limited by its invasiveness and high cost. Therefore, non-invasive, cost-effective, and accurate alternatives are urgently needed.
OBJECTIVE AND DESIGN
This retrospective multi-center plasma proteomics study was performed to identify potential blood-based biomarkers in 36 CRC patients and 26 healthy volunteers by high-resolution mass spectrometry proteomics followed by the validation in an independent CRC cohort (60 CRC patients and 44 healthy subjects) of identified selected biomarkers.
RESULTS
Among the 322 identified plasma proteins, 37 were changed between CRC patients and healthy volunteers and were associated with the complement cascade, cholesterol metabolism, and SERPIN family members. Increased levels in CRC patients of the complement proteins C1QB, C4B, and C5 as well as pro-inflammatory proteins, lipopolysaccharide-binding protein (LBP) and serum amyloid A4, constitutive (SAA4) were revealed for first time. Importantly, increased level of C5 was verified in an independent validation CRC cohort. Increased C4B and C8A levels were correlated with cancer-associated inflammation and CRC progression, while cancer-associated inflammation was linked to the acute-phase reactant leucine-rich alpha-2-glycoprotein 1 (LRG1) and ceruloplasmin. Moreover, a 4-protein signature including C4B, C8A, apolipoprotein C2 (APO) C2, and immunoglobulin heavy constant gamma 2 was changed between early and late CRC stages.
CONCLUSION
Our results suggest that C5 could be a potential biomarker for CRC diagnosis. Further validation studies will aid the application of these new potential biomarkers to improve CRC diagnosis and patient care.
PubMed: 38911905
DOI: 10.1177/11772719241257739 -
EBioMedicine Jun 2024Mapping gut microecological features to serum metabolites (SMs) will help identify functional links between gut microbiome and cardiometabolic health.
BACKGROUND
Mapping gut microecological features to serum metabolites (SMs) will help identify functional links between gut microbiome and cardiometabolic health.
METHODS
This study encompassed 836-1021 adults over 9.7 year in a cohort, assessing metabolic syndrome (MS), carotid atherosclerotic plaque (CAP), and other metadata triennially. We analyzed mid-term microbial metagenomics, targeted fecal and serum metabolomics, host genetics, and serum proteomics.
FINDINGS
Gut microbiota and metabolites (GMM) accounted for 15.1% overall variance in 168 SMs, with individual GMM factors explaining 5.65%-10.1%, host genetics 3.23%, and sociodemographic factors 5.95%. Specifically, GMM elucidated 5.5%-49.6% variance in the top 32 GMM-explained SMs. Each 20% increase in the 32 metabolite score (derived from the 32 SMs) correlated with 73% (95% confidence interval [CI]: 53%-95%) and 19% (95% CI: 11%-27%) increases in MS and CAP incidences, respectively. Among the 32 GMM-explained SMs, sebacic acid, indoleacetic acid, and eicosapentaenoic acid were linked to MS or CAP incidence. Serum proteomics revealed certain proteins, particularly the apolipoprotein family, mediated the relationship between GMM-SMs and cardiometabolic risks.
INTERPRETATION
This study reveals the significant influence of GMM on SM profiles and illustrates the intricate connections between GMM-explained SMs, serum proteins, and the incidence of MS and CAP, providing insights into the roles of gut dysbiosis in cardiometabolic health via regulating blood metabolites.
FUNDING
This study was jointly supported by the National Natural Science Foundation of China, Key Research and Development Program of Guangzhou, 5010 Program for Clinical Research of Sun Yat-sen University, and the 'Pioneer' and 'Leading goose' R&D Program of Zhejiang.
PubMed: 38908099
DOI: 10.1016/j.ebiom.2024.105209 -
Life Science Alliance Sep 2024Apolipoprotein E4, the most important genetic risk factor for Alzheimer's disease, is shown to internalize into neurons and intersect with amyloid-β in...
Apolipoprotein E4, the most important genetic risk factor for Alzheimer's disease, is shown to internalize into neurons and intersect with amyloid-β in endosomes-autophagosomes of neurites and modulate intraneuronal amyloid-β-42.
PubMed: 38906679
DOI: 10.26508/lsa.202402875 -
Environment International Jun 2024Emerging evidence has linked arsenic exposure and metabolic homeostasis, but the mechanism is incompletely understood, especially at relatively low concentrations. In...
Emerging evidence has linked arsenic exposure and metabolic homeostasis, but the mechanism is incompletely understood, especially at relatively low concentrations. In this study, we used a mouse model to evaluate the health impacts and metabolic toxicity of arsenic exposure in drinking water at environmentally relevant levels (0.25 and 1.0 ppm). Our results indicated that arsenic damaged intestinal barrier and induced arsenic accumulation, oxidative stress, and pathological changes in the liver and illum. Interestingly, arsenic increased the hepatic triglyceride (TG) and total cholesterol (TC), while reduced serum TG and TC levels. The liver transcriptome found that arsenic exposure caused transcriptome perturbation and promoted hepatic lipid accumulation by regulating the exogenous fatty acids degradation and apolipoproteins related genes. The serum metabolomics identified 74 and 88 differential metabolites in 0.25 and 1.0 ppm, respectively. The KEGG disease and subcellular location analysis indicated that arsenic induced liver and intestinal diseases, and the mitochondrion might be the target organelle for arsenic-induced toxicity. Co-enrichment of transcriptome and metabolome identified 24 metabolites and 9 genes as metabolic toxicity biomarkers. Moreover, 40 male (20 nonalcoholic fatty liver disease (NAFLD) cases and 20 healthy controls) was further selected to validate our findings. Importantly, the significantly changed L-palmitoylcarnitine, 3-hydroxybutyric acid, 2-hydroxycaproic acid and 6 genes of Hadha, Acadl, Aldh3a2, Cpt1a, Cpt2, and Acox1 were found in the NAFLD cases. The results from integrated multi-omics and chemical-protein network analysis indicated that L-palmitoylcarnitine played a critical role in metabolic toxicity by regulating mitochondrial fatty acids β-oxidation genes (Cpt1a, Cpt2). In conclusion, these findings provided new clues for the metabolic toxicity of arsenic exposure at environmentally relevant levels, which involved in the late-life NAFLD development. Our results also contribute to understanding the human responses and phenotypic changes to this hazardous material exposure in the environment.
PubMed: 38906090
DOI: 10.1016/j.envint.2024.108819 -
Health Science Reports Jun 2024This article explores the association between fractures, particularly in the elderly, and elevated plasma high-density lipoprotein cholesterol (HDL-C) levels. The study...
BACKGROUND
This article explores the association between fractures, particularly in the elderly, and elevated plasma high-density lipoprotein cholesterol (HDL-C) levels. The study challenges the conventional idea of HDL-C as "good cholesterol" by revealing its potential role as a risk factor for fractures. Factors contributing to fractures in the elderly, such as diminishing bone strength due to aging-related tissue breakdown, are discussed. Sedentary lifestyles, low bone mineral density (BMD), and habits like smoking and alcohol consumption compound fracture susceptibility.
MATERIALS AND METHODS
The study delves into mechanisms linking elevated HDL-C to fractures, using data from the ASPREE-Fracturesub-study of the ASPREE trial involving Australian and American participants aged 65 and above.
RESULTS
The study showed that over a 4-year period, elevated HDL-C levels in healthy older people were linked to a 14% higher fracture risk. This revelation expands the understanding of fracture risk factors beyond the established norms.
CONCLUSION
The article emphasizes the need to reconsider HDL-C's traditional role as an indicator of cardiovascular health, particularly in light of medications like Statins and Anacetrapib that raise HDL-C levels. It calls for further exploration into the relationship between HDL-C, fractures at varying sites, and different age groups. Practical implications involve incorporating fracture risk associated with high HDL-C into clinical considerations, alongside advocating lifestyle changes for optimal HDL-C levels. In summary, this study prompts a reevaluation of HDL-C's implications in clinical practice, demanding further investigation into the intricacies of this relationship.
PubMed: 38903661
DOI: 10.1002/hsr2.2187