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The APOE isoforms differentially shape the transcriptomic and epigenomic landscapes of human microglia xenografted into a mouse model of Alzheimer's disease

6 months 3 weeks ago
Microglia play a key role in the response to amyloid beta in Alzheimer's disease (AD). In this context, the major transcriptional response of microglia is the upregulation of APOE, the strongest late-onset AD risk gene. Of its three isoforms, APOE2 is thought to be protective, while APOE4 increases AD risk. We hypothesised that the isoforms change gene regulatory patterns that link back to biological function by shaping microglial transcriptomic and chromatin landscapes. We use RNA- and...
Kitty B Murphy

Whole-genome sequencing analyses suggest novel genetic factors associated with Alzheimer's disease and a cumulative effects model for risk liability

6 months 3 weeks ago
Genome-wide association studies (GWAS) on Alzheimer's disease (AD) have predominantly focused on identifying common variants in Europeans. Here, we performed whole-genome sequencing (WGS) of 1,559 individuals from a Korean AD cohort to identify various genetic variants and biomarkers associated with AD. Our GWAS analysis identified a previously unreported locus for common variants (APCDD1) associated with AD. Our WGS analysis was extended to explore the less-characterized genetic factors...
Jun Pyo Kim

Psychological effects of mountainous environments over the life span and potential implications for healthy ageing: A narrative review

6 months 3 weeks ago
BACKGROUND: Healthy ageing is defined as a process of preserving functional capacity to enable well-being in old age. This concept includes both a physical and a psychological component, which can be positively influenced by spending time in nature and being physically active. Mountainous areas offer diverse opportunities to be physically active in a natural environment. However, little research is available on the psychological effects of mountain environments and mountain sports, particularly...
Benedikt Hösl

Integrated multi-omics analysis reveals immunovascular mechanisms of the placenta-maternal brain axis and lifespan neurobehavior changes in a mouse model of preeclampsia

6 months 3 weeks ago
Preeclampsia (PE) is a hypertensive disorder of pregnancy, among the leading global drivers of maternal morbidity. PE can precipitate neuropsychiatric risk, including for peripartum anxiety, depression, and cognitive problems. To investigate mechanisms underlying psycho-obstetric risk in PE, we examined maternal metabolic, placental, brain, and behavioral changes in our chronic vasopressin (AVP) infusion PE mouse model (C57Bl6/J). Elevated maternal AVP secretion predicts PE in humans, and...
Serena Gumusoglu

ElixirSeeker: A Machine Learning Framework Utilizing Fusion Molecular Fingerprints for the Discovery of Lifespan-Extending Compounds

6 months 3 weeks ago
Despite the growing interest in developing anti-aging drugs, high costs and low success rates of traditional drug discovery methods pose significant challenges. Aging is a complex biological process associated with numerous diseases, making the identification of compounds that can modulate aging mechanisms critically important. Accelerating the discovery of potential anti-aging compounds is essential to overcome these barriers and enhance lifespan and healthspan. Here, we present ElixirSeeker, a...
Yan Pan

Multi-organ metabolome biological age implicates cardiometabolic conditions and mortality risk

6 months 3 weeks ago
Multi-organ biological aging clocks across different organ systems have been shown to predict human disease and mortality. Here, we extend this multi-organ framework to plasma metabolomics, developing five organ-specific metabolome-based biological age gaps (MetBAGs) using 107 plasma non-derivatized metabolites from 274,247 UK Biobank participants. Our age prediction models achieve a mean absolute error of approximately 6 years (0.25
MULTI consortium