Yingxue Ren
A5101905888- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Neurological diseases and metabolism
- Dementia and Cognitive Impairment Research
- Bioinformatics and Genomic Networks
- Cholesterol and Lipid Metabolism
- Amyotrophic Lateral Sclerosis Research
- Genomics and Rare Diseases
- Immune cells in cancer
- Genetic Associations and Epidemiology
- RNA regulation and disease
- Tryptophan and brain disorders
- Single-cell and spatial transcriptomics
- Scientific Computing and Data Management
- Genomics and Phylogenetic Studies
- Neurogenesis and neuroplasticity mechanisms
- Immunotherapy and Immune Responses
- Inflammation biomarkers and pathways
- RNA Research and Splicing
- S100 Proteins and Annexins
- Genetics, Aging, and Longevity in Model Organisms
- Peroxisome Proliferator-Activated Receptors
- Epigenetics and DNA Methylation
- Cerebrovascular and genetic disorders
Mayo Clinic in Florida
2016-2025
Jacksonville College
2024
WinnMed
2018-2024
Beijing Tsinghua Chang Gung Hospital
2024
Tsinghua University
2024
Quantitative BioSciences
2023
Center for Drug Evaluation and Research
2020
United States Food and Drug Administration
2020
Mayo Clinic
2018
National Center for Supercomputing Applications
2017
Abstract APOE4 is the strongest genetic risk factor associated with late-onset Alzheimer’s disease (AD). To address underlying mechanism, we develop cerebral organoid models using induced pluripotent stem cells (iPSCs) APOE ε3/ε3 or ε4/ε4 genotype from individuals either normal cognition AD dementia. Cerebral organoids patients carrying show greater apoptosis and decreased synaptic integrity. While patient-derived have increased levels of Aβ phosphorylated tau compared to healthy...
Sepsis is a prevalent health issue that can lead to central nervous system (CNS) inflammation with long-term behavioral and cognitive alterations. Using unbiased proteomic profiling of over 100 different cytokines, we found Lipocalin-2 (LCN2) was the most substantially elevated protein in CNS after peripheral administration lipopolysaccharide (LPS). To determine whether high level LCN2 protective or deleterious, challenged Lcn2−/− mice LPS determined effects on behavior neuroinflammation. At...
The apolipoprotein E (
Apolipoprotein E (APOE) genetic variants have been shown to modify Alzheimer’s disease (AD) risk. We previously identified an APOE3 variant (APOE3-V236E), named APOE3-Jacksonville (APOE3-Jac), associated with healthy brain aging and reduced risk for AD dementia Lewy bodies (DLB). Herein, we resolved the functional mechanism by which APOE3-Jac reduces APOE aggregation enhances its lipidation in human brains, as well cellular biochemical assays. Compared APOE3, expression of astrocytes...
TREM2 is exclusively expressed by microglia in the brain and strongly linked to risk for Alzheimer’s disease (AD). As microglial responses modulated are central AD pathogenesis, enhancing signaling has been explored as an therapeutic strategy. However, effective window targeting unclear. Here, using microglia-specific inducible mouse models overexpressing human wild-type (TREM2-WT) or R47H variant (TREM2-R47H), we show that TREM2-WT expression reduces amyloid deposition neuritic dystrophy...
Abstract INTRODUCTION Loss‐of‐function variants of the ABCA7 gene are associated with an increased risk Alzheimer's disease (AD). How neuronal contributes to AD pathogenesis is unknown. METHODS Using neuron‐specific Abca7 KO mice (n −/− ) or without 5×FAD amyloid model background and post mortem brains, we investigated AD‐related phenotypes through comprehensive approaches including transcriptomics lipidomics. RESULTS Lipidomics analysis detected altered lipid profiles in brains synaptosomes...
Carrying premature termination codons in 1 allele of the ABCA7 gene is associated with an increased risk for Alzheimer’s disease (AD). While primary function to regulate transport phospholipids and cholesterol, also involved maintaining homeostasis immune system. Since inflammatory pathways causatively or consequently participate AD pathogenesis, we studied effects Abca7 haplodeficiency mice on brain responses under acute chronic conditions. When inflammation was induced through peripheral...
Objective: The ε4 allele of the APOE gene ( APOE4 ) is strongest genetic risk factor for Alzheimer disease when compared with common ε3 allele. Although there has been significant progress in understanding how apoE4 (apolipoprotein E4) drives amyloid pathology, its effects on amyloid-independent pathways, particular cerebrovascular integrity and function, are less clear. Approach Results: Here, we show that brain pericytes, mural cells capillary walls, differentially modulate endothelial...
Abstract Genetic variants that define two distinct haplotypes at the TMEM106B locus have been implicated in multiple neurodegenerative diseases and healthy brain ageing. In frontotemporal dementia (FTD), high expressing risk haplotype was shown to increase susceptibility for FTD with TDP-43 inclusions (FTD-TDP) modify disease penetrance progranulin mutation carriers (FTD-GRN). To elucidate biological function of determine whether lowering may be a viable therapeutic strategy, we performed...
Abstract ABCA7 loss-of-function variants are associated with increased risk of Alzheimer’s disease (AD). Using knockout human iPSC models generated CRISPR/Cas9, we investigated the impacts deficiency on neuronal metabolism and function. Lipidomics revealed that mitochondria-related phospholipids, such as phosphatidylglycerol cardiolipin were reduced in ABCA7-deficient iPSC-derived cortical organoids. Consistently, deficiency-induced alterations mitochondrial morphology accompanied by ATP...
The immune system substantially influences age-related cognitive decline and Alzheimer's disease (AD) progression, affected by genetic environmental factors. In a Mayo Clinic Study of Aging cohort, we examined how risk factors like APOE genotype, age, sex affect inflammatory molecules AD biomarkers in cerebrospinal fluid (CSF). Among cognitively unimpaired individuals over 65 (
Abstract The majority of the clinico-pathological variability observed in patients harboring a repeat expansion C9orf72-SMCR8 complex subunit ( C9orf72 ) remains unexplained. This expansion, which represents most common genetic cause frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND), results loss expression generation RNA foci dipeptide (DPR) proteins. protein itself plays role vesicular transport, serving as guanine nucleotide exchange factor that regulates GTPases. To...
Tumors acquire numerous mutations during development and progression. When translated into proteins, these give rise to neoantigens that can be recognized by T cells generate antibodies, representing an exciting direction of cancer immunotherapy. While have been reported in many types, the profiling often focused on class-I subtype are presented CD8 + cells, relationship between neoantigen load clinical outcomes was inconsistent among types. In this study, we described informatics workflow,...
APOE4 is a strong genetic risk factor for Alzheimer's disease and Dementia with Lewy bodies; however, how its expression impacts pathogenic pathways in human-relevant system not clear. Here using human iPSC-derived cerebral organoid models, we find that APOE deletion increases α-synuclein (αSyn) accumulation accompanied synaptic loss, reduction of GBA levels, lipid droplet dysregulation intracellular organelles. These phenotypes are partially rescued by exogenous apoE2 apoE3, but apoE4....
Cerebrovasculature is critical in maintaining brain homeostasis; its dysregulation often leads to vascular cognitive impairment and dementia (VCID) during aging. VCID the second most prevalent cause of elderly, after Alzheimer's disease (AD), with frequent cooccurrence AD. While multiple factors are involved pathogenesis AD VCID, APOE4 increases risk for both diseases. A major apolipoprotein E (apoE) receptor, low-density lipoprotein receptor-related protein 1 (LRP1), abundantly expressed...
Abstract Background The apolipoprotein E ( APOE ) gene is the strongest genetic risk factor for Alzheimer’s disease (AD); however, how it modulates brain homeostasis not clear. apoE protein a major lipid carrier in transporting lipids such as cholesterol among different cell types. Methods We generated three-dimensional (3-D) cerebral organoids from human parental iPSC lines and its isogenic -deficient −/− line. To elucidate cell-type-specific effects of deficiency organoids, we performed...
ABSTRACT Loss-of-function mutations in the genes encoding PINK1 and PRKN result early-onset Parkinson disease (EOPD). Together encoded enzymes direct a neuroprotective pathway that ensures elimination of damaged mitochondria via autophagy. We performed genome-wide high content imaging miRNA screen for inhibitors PINK1-PRKN identified all three members family 29 (miR-29). Using RNAseq we target found siRNA against ATG9A phenocopied effects miR-29 inhibited initiation mitophagy. Furthermore,...