Background: APOE polymorphism and the Kynurenine pathway (KP) are associated with many disorders, but little is known about associations between APOE polymorphism and the KP. This study explored the associations between the KP and APOE polymorphism in disorders associated with APOE polymorphism and changes in the KP.
Methods: Subjects with morbid obesity before and after bariatric surgery (numbers 139 and 95, respectively), depression (number 49), and unspecified neurological symptoms (number 39) were included. The following grouping of the APOE genotypes was used: E2 = ɛ2ɛ2 + ɛ2ɛ3, E3 = ɛ3ɛ3 + ɛ2ɛ4, and E4 = ɛ3ɛ4 + ɛ4ɛ4. The KP metabolites Tryptophan, Kynurenine, Kynurenic acid, Quinolinic acid, and Xanthurenic acid were quantified in serum.
Results: The main findings were a significant positive association between E3 and Quinolinic acid (difference between E3 and E2E4: 12.0 (3.5; 18.6) ng/mL); = 0.005), and a negative association between E4 and Kynurenine (difference between E4 and E2E3: -31.3 (-54.2; -3.2) ng/mL; = 0.008). Quinolinic acid has been ascribed neurotoxic and inflammatory effects, and Kynurenine is a marker of inflammation.
Conclusions: The findings indicate that APOE polymorphism might cause changes in the KP that contribute to the disease. Inflammation could be the link between APOE and the KP.
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http://dx.doi.org/10.3390/genes14101955 | DOI Listing |
EBioMedicine
January 2025
Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore, Singapore; Department of Biochemistry and Precision Medicine Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Electronic address:
Background: Apolipoproteins as an integral part of lipoproteins are crucial for the transport and metabolism of lipids. However, there is a lack of longitudinal studies to quantify the concentrations of maternal apolipoproteins from preconception to postpartum and their associations with maternal metabolic health and offspring birth outcomes.
Methods: Quantification of apolipoproteins was performed on maternal plasma samples (N = 243 trios) collected at preconception, 26-28 weeks' pregnancy, and three months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study.
Alzheimers Dement (N Y)
January 2025
Indiana Alzheimer Disease Research Center and Center for Neuroimaging, Department of Radiology and Imaging Sciences Indiana University School of Medicine Indianapolis Indiana USA.
Introduction: The exponential growth of genomic datasets necessitates advanced analytical tools to effectively identify genetic loci from large-scale high throughput sequencing data. This study presents Deep-Block, a multi-stage deep learning framework that incorporates biological knowledge into its AI architecture to identify genetic regions as significantly associated with Alzheimer's disease (AD). The framework employs a three-stage approach: (1) genome segmentation based on linkage disequilibrium (LD) patterns, (2) selection of relevant LD blocks using sparse attention mechanisms, and (3) application of TabNet and Random Forest algorithms to quantify single nucleotide polymorphism (SNP) feature importance, thereby identifying genetic factors contributing to AD risk.
View Article and Find Full Text PDFInt J Geriatr Psychiatry
January 2025
Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China.
Background: Apolipoprotein E (ApoE) ε4 genotype is a well-known risk factor for Alzheimer's disease (AD). However, its effect on predicting cognitive decline in individuals without dementia and its association with age are unclear.
Objective: To investigate the relationship between ApoE polymorphism and risk of cognitive decline and dementia incidence in the elderly without dementia.
Mol Neurobiol
January 2025
Department of Neurology, Huai'an First People's Hospital, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, No.1 Huanghe West Road, Huai'an, 223300, Jiangsu, China.
A comprehensive genome-wide association study (GWAS) has validated the identification of the Plexin-A 4 (PLXNA4) gene as a novel susceptibility factor for Alzheimer's disease (AD). Nonetheless, the precise role of PLXNA4 gene polymorphisms in the pathophysiology of AD remains to be established. Consequently, this study is aimed at exploring the relationship between PLXNA4 gene polymorphisms and neuroimaging phenotypes intimately linked to AD.
View Article and Find Full Text PDFNutrients
January 2025
Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Circulating glycine levels have been associated with reduced risk of coronary artery disease (CAD) in humans but these associations have not been observed in all studies. We evaluated whether the relationship between glycine levels and atherosclerosis was causal using genetic analyses in humans and feeding studies in mice. Serum glycine levels were evaluated for association with risk of CAD in the UK Biobank.
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