A growing amount of data has implicated the gene in the risk for Alzheimer's disease (AD), neurodegeneration, and accelerated aging. No studies have investigated the relationship of rs2075650 ('650 on the structural complexity of the brain or plasma markers of neurodegeneration. We used a comprehensive approach to quantify the impact of '650 on brain morphology and multiple cortical attributes in cognitively unimpaired (CU) individuals. We also tested whether the presence of the risk allele, G, of '650 was associated with plasma markers of amyloid, tau, and neurodegeneration and if there were interactions with age and sex, controlling for the effects of ε4. We found that the '650 G-allele was associated with decreased sulcal depth, increased gyrification index, and decreased gray matter volume. NfL, GFAP, and pTau181 had independent and age-associated increases in individuals with a G-allele. Our data suggest that '650 is associated with aging-related plasma biomarkers and brain structure variation in temporal-limbic circuits.
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http://dx.doi.org/10.1016/j.nbas.2024.100134 | DOI Listing |
Expert Rev Proteomics
January 2025
Skolkovo Institute of Science and Technology, Moscow, Russian Federation.
Introduction: Identifying early risks of developing Alzheimer's disease (AD) is a major challenge as the number of patients with AD steadily increases and requires innovative solutions. Current molecular diagnostic modalities, such as cerebrospinal fluid (CSF) testing and positron emission tomography (PET) imaging, exhibit limitations in their applicability for large-scale screening. In recent years, there has been a marked shift toward the development of blood plasma-based diagnostic tests, which offer a more accessible and clinically viable alternative for widespread use.
View Article and Find Full Text PDFScand J Gastroenterol
January 2025
Norwegian PSC Research Centre, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Objectives: Indications of mitochondrial dysfunction are commonly seen in liver diseases, but data are scarce in primary sclerosing cholangitis (PSC). Analyzing circulating and liver-resident molecules indirectly reflecting mitochondrial dysfunction, we aimed to comprehensively characterize this deficit in PSC, and whether this was PSC specific or associated with cholestasis.
Materials And Methods: We retrospectively included plasma from 191 non-transplant patients with large-duct PSC and 100 healthy controls and explanted liver tissue extracts from 24 PSC patients and 18 non-cholestatic liver disease controls.
Background: Recent reports suggest increased myocardial iNOS expression leads to excessive protein -nitrosylation, contributing to the pathophysiology of HFpEF. However, the relationship between NO bioavailability, dynamic regulation of protein -nitrosylation by trans- and de-nitrosylases, and HFpEF pathophysiology has not been elucidated. Here, we provide novel insights into the delicate interplay between NO bioavailability and protein -nitrosylation in HFpEF.
View Article and Find Full Text PDFFront Aging Neurosci
December 2024
Department of Geriatrics, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, China.
Objectives: Glutathione S-transferase alpha (GSTα) is an important antioxidant enzyme closely associated with the onset and progression of neurodegenerative diseases. The alterations in GSTα protein levels associated with Alzheimer's disease and their impact on cognitive abilities remain unclear. Thus, investigating the fluctuations of GSTα protein levels in mild cognitive impairment (MCI) and Alzheimer's disease (AD) is essential.
View Article and Find Full Text PDFIncreasing evidence suggests the involvement of metabolic alterations in neurological disorders, including Alzheimer's disease (AD), and highlights the significance of the peripheral metabolome, influenced by genetic factors and modifiable environmental exposures, for brain health. In this study, we examined 1,387 metabolites in plasma samples from 1,082 dementia-free middle-aged participants of the population-based Rotterdam Study. We assessed the relation of metabolites with general cognition (G-factor) and magnetic resonance imaging (MRI) markers using linear regression and estimated the variance of these metabolites explained by genes, gut microbiome, lifestyle factors, common clinical comorbidities, and medication using gradient boosting decision tree analysis.
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