Biomarkers.

Background: The apolipoprotein E (ApoE) Ɛ4 allele is associated with a significant risk for both late-onset Alzheimer's Disease (AD) development and cerebral amyloidosis, but the degree to which cerebrospinal fluid (CSF) apoE glycosylation affects disease progression is unclear. The objective of this study was to examine the relationship of CSF apoE glycosylation with t-tau, p-tau181, and Aβ1-42 CSF levels, and to delineate the effect of the APOE4+ genotype (vs E4-) on glycosylation.

Method: Total glycosylation and apoE isoform-specific glycosylation were analyzed in baseline plasma and CSF samples from a longitudinal cohort of older individuals (n=188, ages 55 - 89) from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

Public Health.

Background: Apolipoprotein E (APOE) is a known genetic risk factor for dementia. Midlife cardiovascular risk factors are associated with lower cognitive performance and increased dementia risk. However, little is known whether cardiovascular risk factors mediate or modify the associations between APOE and cognitive decline in late-life.

Drug Development.

Background: ABCA1-mediated cholesterol transport is a central feature in many lipid- dependent diseases including APOE4-associated Alzheimer's disease and atherosclerosis-CVD. ABCA1 upregulation of RNA transcription by nuclear factors (LXR, RXR) have been associated with liver side-effects because of the common promotor element for ABCA1 and Fatty Acid Synthase. The ABCA1 agonist CS6253, derived from the C-terminal of apoE was designed to stabilize and enhance ABCA1 function, thereby providing a safe alternative to transcriptional upregulation.

Increased cerebrospinal fluid and plasma apoE glycosylation is associated with reduced levels of Alzheimer's disease biomarkers.

The apolipoprotein E ( ) ε4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). ApoE is glycosylated with an O-linked Core-1 sialylated glycan at several sites, yet the impact and function of this glycosylation on AD biomarkers remains unclear. We examined apoE glycosylation in a cohort of cerebrospinal fluid (CSF, n=181) and plasma (n= 178) samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) stratified into 4 groups: cognitively normal (CN), Mild Cognitive Impairment (MCI), progressors and non-progressors based on delayed word recall performance over 4 years.

Microglia States are Susceptible to Senescence and Cholesterol Dysregulation in Alzheimer's Disease.

Cellular senescence is a major contributor to aging-related degenerative diseases, including Alzheimer's disease (AD) but much less is known on the key cell types and pathways driving mechanisms of senescence in the brain. We hypothesized that dysregulated cholesterol metabolism is central to cellular senescence in AD. We analyzed whole transcriptomic data and utilized single-cell RNA seq integration techniques to unveil the convoluted cell-type-specific and sub-cell-type-state-specific senescence pathologies in AD using both ROSMAP and Sea-AD datasets.

Stress Changes the Bacterial Biomolecular Condensate Material State and Shifts Function from mRNA Decay to Storage.

Bacterial ribonucleoprotein bodies (BR-bodies) are dynamic biomolecular condensates that play a pivotal role in RNA metabolism. We investigated how BR-bodies significantly influence mRNA fate by transitioning between liquid- and solid-like states in response to stress. With a combination of single-molecule and bulk fluorescence microscopy, biochemical assays, and quantitative analyses, we determine that BR-bodies promote efficient mRNA decay in a liquid-like condensate during exponential growth.

Development of Calcium-Dependent Phospholipase A2 Inhibitors to Target Cellular Senescence and Oxidative Stress in Neurodegenerative Diseases.

Cellular senescence is a critical process underlying aging and is associated with age-related diseases such as Alzheimer's disease. Lipids are implicated in cellular senescence. Fatty acids, particularly eicosanoids, have been associated with various forms of senescence and inflammation, and the associated reactive oxygen species production has been proposed as a therapeutic target for mitigating senescence.

Seroprevalence and detection of Human herpesvirus-8 (HHV-8) among healthy blood donors residing in Qatar.

Background: Human herpesvirus 8 (HHV-8) is a critical causative agent behind Kaposi sarcoma (KS), an oncogenic disease with profound consequences in immunocompromised individuals. Studies suggested HHV-8 seroprevalence in healthy populations is uncommon, but comprehensive investigations within the Middle East region remain scarce. This study aimed to bridge this knowledge gap by meticulously assessing HHV-8 seroprevalence among healthy blood donors in Qatar, leveraging serological methodologies and PCR.

Evaluation of the mindray CL900i CLIA HIV Ag/Ab combo assay for sensitive and specific HIV screening compared to established methods.

Architect-HIV Ag/Ab combo chemiluminescence assay is globally recognized for its sensitivity but has a notable false-positive rate. In this study, we aim to evaluate the performance of a new cost-effective screening alternative, the chemiluminescence Ag/Ab combo assay (CL-900i-HIV) from Mindray, China. We selected 195 archived samples categorized according to the INNO-LIA™ HIV I/II, the gold standard confirmatory assay.

APOE ε4 and Dietary Patterns in Relation to Cognitive Function: An Umbrella Review of Systematic Reviews.

Context: Carrying the apolipoprotein ε4 allele (APOE ε4) is the strongest genetic risk factor for late-onset Alzheimer's disease. There is some evidence suggesting that APOE ε4 may modulate the influence of diet on cognitive function.

Objective: This umbrella review of systematic reviews evaluates the existing literature on the effect of dietary interventions on cognitive and brain-imaging outcomes by APOE status.

Enhancing Influenza Detection through Integrative Machine Learning and Nasopharyngeal Metabolomic Profiling: A Comprehensive Study.

Nasal and nasopharyngeal swabs are commonly used for detecting respiratory viruses, including influenza, which significantly alters host cell metabolites. This study aimed to develop a machine learning model to identify biomarkers that differentiate between influenza-positive and -negative cases using clinical metabolomics data. A publicly available dataset of 236 nasopharyngeal samples screened via liquid chromatography-quadrupole time-of-flight (LC/Q-TOF) mass spectrometry was used.

APEX2 proximity labeling of RNA in bacteria.

Studies over the past several years have shown that distinct RNAs can be targeted to subcellular locations in bacterial cells. The ability to investigate localized RNAs in bacteria is currently limited to imaging-based approaches or to laborious procedures to isolate ribonucleoprotein complexes by grad-seq, HITS-CLIP, or Rloc-seq. However, a major challenge in studying mRNA localization in bacterial cells is that bacterial mRNAs typically last for only a few minutes in the cell, while experiments to investigate their localization or interaction partners can take much longer.

BNT162b2 Versus mRNA-1273 Vaccines: Comparative Analysis of Long-Term Protection Against SARS-CoV-2 Infection and Severe COVID-19 in Qatar.

Background: This study provides a head-to-head comparison of the protection provided by the BNT162b2 and mRNA-1273 vaccines against SARS-CoV-2 infection and against severe COVID-19, covering primary series and third dose/booster vaccinations over up to 3 years of follow-up, both before and after the emergence of the omicron variant.

Methods: Two national, matched, retrospective cohort studies were conducted on Qatar's vaccinated population from December 16, 2020, to February 18, 2024. Subgroup analyses by pre-vaccination SARS-CoV-2 infection history, as well as sensitivity analyses, were also conducted.

Lower entorhinal cortex thickness is associated with greater financial exploitation vulnerability in cognitively unimpaired older adults.

Research suggests that increased financial exploitation vulnerability due to declining decision making may be an early behavioral manifestation of brain changes occurring in preclinical Alzheimer's disease. One of the earliest documented brain changes during the preclinical phase is neurodegeneration in the entorhinal cortex. The objective of the current study was to examine the association between a measure of financial exploitation vulnerability and thickness in the entorhinal cortex in 97 cognitively unimpaired older adults.

Combining Gram stain and 16S qPCR improved diagnostic accuracy for suspected pneumonia and could become a new metric in the rapid diagnosis of lower respiratory tract infections.

The frequency of multidrug-resistant organisms (MDROs) in hospitals and the risk of delaying effective treatment result in the culture of respiratory secretions for nearly all patients with suspected pneumonia. Culture delays contribute to over prescribing and use of broader spectrum antibiotics. The need for improved rapid diagnostics for early assessment of suspected hospital pneumonia.

A narrative review on the role of cytokines in the pathogenesis and treatment of familial Mediterranean fever: an emphasis on pediatric cases.

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease characterized by an early onset of recurrent fever and serositis episodes. FMF is caused by mutations in the gene which encodes the pyrin protein, an IL-1β mediated inflammation regulator. Recent findings have identified a plethora of molecules and pathways involved in the regulation of inflammation and innate immunity, hence increasing our understanding of the etiology and inflammatory nature of FMF.

Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference.

Introduction: The apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid-beta and tau pathologies but also lipid and energy metabolism, neuroinflammation, cerebral vascular health, and sex-dependent disease manifestations. Furthermore, ancestral background may significantly impact the link between APOE and AD, underscoring the need for more inclusive research.

Evaluation of Efficacy of Surface Coated versus Encapsulated Influenza Antigens in Mannose-Chitosan Nanoparticle-Based Intranasal Vaccine in Swine.

This study focuses on the development and characterization of an intranasal vaccine platform using adjuvanted nanoparticulate delivery of swine influenza A virus (SwIAV). The vaccine employed whole inactivated H1N2 SwIAV as an antigen and STING-agonist ADU-S100 as an adjuvant, with both surface adsorbed or encapsulated in mannose-chitosan nanoparticles (mChit-NPs). Optimization of mChit-NPs included evaluating size, zeta potential, and cytotoxicity, with a 1:9 mass ratio of antigen to NP demonstrating high loading efficacy and non-cytotoxic properties suitable for intranasal vaccination.

Comparable antibody levels in heterologous and homologous mRNA COVID-19 vaccination, with superior neutralizing and IgA antibody responses in mRNA homologous boosting.

Background: Priming with two doses of AZD1222 (Oxford-AstraZeneca; ChAd) followed by a third mRNA vaccine boosting is considered in several countries, yet comparisons between heterologous and homologous booster efficacy remain unexplored.

Aim: To evaluate and contrast the immunogenicity of homologous and heterologous boosting regimens.

Method: The study examined antibody responses in 1113 subjects, comprising 895 vaccine-naïve individuals across different vaccination strategies (partial, primary series, heterologous booster, homologous booster) and 218 unvaccinated, naturally infected individuals.

Metabolic predictors of COVID-19 mortality and severity: a survival analysis.

Introduction: The global healthcare burden of COVID-19 pandemic has been unprecedented with a high mortality. Metabolomics, a powerful technique, has been increasingly utilized to study the host response to infections and to understand the progression of multi-system disorders such as COVID-19. Analysis of the host metabolites in response to SARS-CoV-2 infection can provide a snapshot of the endogenous metabolic landscape of the host and its role in shaping the interaction with SARS-CoV-2.

Cellular senescence induced by cholesterol accumulation is mediated by lysosomal ABCA1 in APOE4 and AD.

Background: Cellular senescence is a hallmark of aging and has been implicated in Alzheimer's disease (AD) pathogenesis. Cholesterol accumulation drives cellular senescence; however, the underlying mechanisms are unclear. ATP-binding cassette transporter A1 (ABCA1) plays an important role in cholesterol homeostasis.