Locus specific endogenous retroviral expression associated with Alzheimer's disease.

Introduction: Human endogenous retroviruses (HERVs) are transcriptionally-active remnants of ancient retroviral infections that may play a role in Alzheimer's disease.

Methods: We combined two, publicly available RNA-Seq datasets with a third, novel dataset for a total cohort of 103 patients with Alzheimer's disease and 45 healthy controls. We use telescope to perform HERV quantification for these samples and simultaneously perform gene expression analysis.

The genome of a giant (trevally): .

, commonly known as giant kingfish or giant trevally, is a large, reef-associated apex predator. It is a prized sportfish, targeted throughout its tropical and subtropical range in the Indian and Pacific Oceans. It also gained significant interest in aquaculture due to its unusual freshwater tolerance.

Comorbidity and Cancer Disease Rates among Those at High-Risk for Alzheimer's Disease: A Population Database Analysis.

(1) Importance: Alzheimer's disease (AD) is complex and only partially understood. Analyzing the relationship between other more treatable or preventable diseases and AD may help in the prevention and the eventual development of treatments for AD. Risk estimation in a high-risk population, rather than a population already affected with AD, may reduce some bias in risk estimates.

The Polygenic Risk Score Knowledge Base offers a centralized online repository for calculating and contextualizing polygenic risk scores.

The process of identifying suitable genome-wide association (GWA) studies and formatting the data to calculate multiple polygenic risk scores on a single genome can be laborious. Here, we present a centralized polygenic risk score calculator currently containing over 250,000 genetic variant associations from the NHGRI-EBI GWAS Catalog for users to easily calculate sample-specific polygenic risk scores with comparable results to other available tools. Polygenic risk scores are calculated either online through the Polygenic Risk Score Knowledge Base (PRSKB; https://prs.

Web-Based Protein Interactions Calculator Identifies Likely Proteome Coevolution with Alzheimer's Disease-Associated Proteins.

Protein-protein functional interactions arise from either transitory or permanent biomolecular associations and often lead to the coevolution of the interacting residues. Although mutual information has traditionally been used to identify coevolving residues within the same protein, its application between coevolving proteins remains largely uncharacterized. Therefore, we developed the Protein Interactions Calculator (PIC) to efficiently identify coevolving residues between two protein sequences using mutual information.

The Ramp Atlas: facilitating tissue and cell-specific ramp sequence analyses through an intuitive web interface.

Ramp sequences occur when the average translational efficiency of codons near the 5' end of highly expressed genes is significantly lower than the rest of the gene sequence, which counterintuitively increases translational efficiency by decreasing downstream ribosomal collisions. Here, we show that the relative codon adaptiveness within different tissues changes the existence of a ramp sequence without altering the underlying genetic code. We present the first comprehensive analysis of tissue and cell type-specific ramp sequences and report 3108 genes with ramp sequences that change between tissues and cell types, which corresponds with increased gene expression within those tissues and cells.

Knowledge Gaps, Challenges, and Opportunities in Health and Prevention Research for Asian Americans, Native Hawaiians, and Pacific Islanders: A Report From the 2021 National Institutes of Health Workshop.

Asian Americans (AsA), Native Hawaiians, and Pacific Islanders (NHPI) comprise 7.7% of the U.S.

Pairwise Correlation Analysis of the Alzheimer's Disease Neuroimaging Initiative (ADNI) Dataset Reveals Significant Feature Correlation.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) contains extensive patient measurements (e.g., magnetic resonance imaging [MRI], biometrics, RNA expression, etc.

GenoRisk: A polygenic risk score for Alzheimer's disease.

Introduction: Recent clinical trials are considering inclusion of more than just apolipoprotein E () ε4 genotype as a way of reducing variability in analysis of outcomes.

Methods: Case-control data were used to compare the capacity of age, sex, and 58 Alzheimer's disease (AD)-associated single nucleotide polymorphisms (SNPs) to predict AD status using several statistical models. Model performance was assessed with Brier scores and tenfold cross-validation.

De novo genome assembly of the marine teleost, bluefin trevally (Caranx melampygus).

The bluefin trevally, Caranx melampygus, also known as the bluefin kingfish or bluefin jack, is known for its remarkable, bright-blue fins. This marine teleost is a widely prized sportfish, but few resources have been devoted to the genomics and conservation of this species because it is not targeted by large-scale commercial fisheries. Population declines from recreational and artisanal overfishing have been observed in Hawai'i, USA, resulting in both an interest in aquaculture and concerns about the long-term conservation of this species.

Analysis of genes (TMEM106B, GRN, ABCC9, KCNMB2, and APOE) implicated in risk for LATE-NC and hippocampal sclerosis provides pathogenetic insights: a retrospective genetic association study.

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is the most prevalent subtype of TDP-43 proteinopathy, affecting up to 1/3rd of aged persons. LATE-NC often co-occurs with hippocampal sclerosis (HS) pathology. It is currently unknown why some individuals with LATE-NC develop HS while others do not, but genetics may play a role.

Analysis of high-risk pedigrees identifies 11 candidate variants for Alzheimer's disease.

Introduction: Analysis of sequence data in high-risk pedigrees is a powerful approach to detect rare predisposition variants.

Methods: Rare, shared candidate predisposition variants were identified from exome sequencing 19 Alzheimer's disease (AD)-affected cousin pairs selected from high-risk pedigrees. Variants were further prioritized by risk association in various external datasets.

Alzheimer's disease alters oligodendrocytic glycolytic and ketolytic gene expression.

Introduction: Sporadic Alzheimer's disease (AD) is strongly correlated with impaired brain glucose metabolism, which may affect AD onset and progression. Ketolysis has been suggested as an alternative pathway to fuel the brain.

Methods: RNA-seq profiles of post mortem AD brains were used to determine whether dysfunctional AD brain metabolism can be determined by impairments in glycolytic and ketolytic gene expression.

A comprehensive analysis of the phylogenetic signal in ramp sequences in 211 vertebrates.

Ramp sequences increase translational speed and accuracy when rare, slowly-translated codons are found at the beginnings of genes. Here, the results of the first analysis of ramp sequences in a phylogenetic construct are presented. Ramp sequences were compared from 247 vertebrates (114 Mammalian and 133 non-mammalian), where the presence and absence of ramp sequences was analyzed as a binary character in a parsimony and maximum likelihood framework.

CUBAP: an interactive web portal for analyzing codon usage biases across populations.

Synonymous codon usage significantly impacts translational and transcriptional efficiency, gene expression, the secondary structure of both mRNA and proteins, and has been implicated in various diseases. However, population-specific differences in codon usage biases remain largely unexplored. Here, we present a web server, https://cubap.

Distinct clinicopathologic clusters of persons with TDP-43 proteinopathy.

To better understand clinical and neuropathological features of TDP-43 proteinopathies, data were analyzed from autopsied research volunteers who were followed in the National Alzheimer's Coordinating Center (NACC) data set. All subjects (n = 495) had autopsy-proven TDP-43 proteinopathy as an inclusion criterion. Subjects underwent comprehensive longitudinal clinical evaluations yearly for 6.

Predicting Clinical Dementia Rating Using Blood RNA Levels.

The Clinical Dementia Rating (CDR) is commonly used to assess cognitive decline in Alzheimer's disease patients and is included in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. We divided 741 ADNI participants with blood microarray data into three groups based on their most recent CDR assessment: cognitive normal (CDR = 0), mild cognitive impairment (CDR = 0.5), and probable Alzheimer's disease (CDR ≥ 1.

Identification and genomic analysis of pedigrees with exceptional longevity identifies candidate rare variants.

Background: Longevity as a phenotype entails living longer than average and typically includes living without chronic age-related diseases. Recently, several common genetic components to longevity have been identified. This study aims to identify additional genetic variants associated with longevity using unique and powerful analyses of pedigrees with a statistical excess of healthy elderly individuals identified in the Utah Population Database (UPDB).

Genome-wide association study of rate of cognitive decline in Alzheimer's disease patients identifies novel genes and pathways.

Introduction: Variability exists in the disease trajectories of Alzheimer's disease (AD) patients. We performed a genome-wide association study to examine rate of cognitive decline (ROD) in patients with AD.

Methods: We tested for interactions between genetic variants and time since diagnosis to predict the ROD of a composite cognitive score in 3946 AD cases and performed pathway analysis on the top genes.

Atypical chemokine receptor ACKR2-V41A has decreased CCL2 binding, scavenging, and activation, supporting sustained inflammation and increased Alzheimer's disease risk.

A recent genome-wide association study (GWAS) of 59 cerebrospinal fluid (CSF) proteins with a connection to Alzheimer's disease (AD) demonstrated an association between increased levels of chemokine ligand 2 (CCL2) with an atypical chemokine receptor chemokine-binding protein 2 variant V41A (ACKR2-V41A; rs2228467). High levels of CCL2 are associated with increased risk of AD development as well as other inflammatory diseases. In this study we characterized the biological function of the ACKR2-V41A receptor compared to the wild type allele by measuring its ligand binding affinity, CCL2 scavenging efficiency, and cell activation sensitivity.

Codon Pairs are Phylogenetically Conserved: A comprehensive analysis of codon pairing conservation across the Tree of Life.

Identical codon pairing and co-tRNA codon pairing increase translational efficiency within genes when two codons that encode the same amino acid are translated by the same tRNA before it diffuses from the ribosome. We examine the phylogenetic signal in both identical and co-tRNA codon pairing across 23 428 species using alignment-free and parsimony methods. We determined that conserved codon pairing typically has a smaller window size than the length of a ribosome, and codon pairing tracks phylogenies across various taxonomic groups.

Failure to detect synergy between variants in transferrin and hemochromatosis and Alzheimer's disease in large cohort.

Alzheimer's disease (AD) is the most common cause of dementia and, despite decades of effort, there is no effective treatment. In the last decade, many association studies have identified genetic markers that are associated with AD status. Two of these studies suggest that an epistatic interaction between variants rs1049296 in the transferrin (TF) gene and rs1800562 in the homeostatic iron regulator (HFE) gene, commonly known as hemochromatosis, is in genetic association with AD.

Interaction Between Physical Activity and Genes Related to Neurotrophin Signaling in Late-Life Cognitive Performance: The Cache County Study.

Research indicates that lifestyle and genetic factors influence the course of cognitive impairment in aging, but their interactions have not been well-examined. This study examined the relationship between physical activity and genotypes related to brain-derived neurotrophic factor (BDNF) in predicting cognitive performance in a sample of older adults with up to 12 years of follow-up. Physical activity levels (sedentary, light, and moderate/vigorous) were determined for the sample of 3,591 participants (57% female) without dementia.