A5100754994- Alzheimer's disease research and treatments
- Pituitary Gland Disorders and Treatments
- Neurological Disease Mechanisms and Treatments
- Glioma Diagnosis and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Neuroimaging Techniques and Applications
- Adrenal Hormones and Disorders
- Dementia and Cognitive Impairment Research
- S100 Proteins and Annexins
- Functional Brain Connectivity Studies
- Cerebrovascular and Carotid Artery Diseases
- Cancer, Hypoxia, and Metabolism
- MRI in cancer diagnosis
- Coronary Interventions and Diagnostics
- Birth, Development, and Health
- Sleep and related disorders
- Biochemical effects in animals
- Anesthesia and Neurotoxicity Research
- Atherosclerosis and Cardiovascular Diseases
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Gestational Diabetes Research and Management
- Metabolism, Diabetes, and Cancer
- Lipoproteins and Cardiovascular Health
- Cerebrospinal fluid and hydrocephalus
- Cholesterol and Lipid Metabolism
Wayne State University
2024-2025
Shanghai Jiao Tong University
2006-2024
Ruijin Hospital
2016-2024
China Tobacco
2024
Washington University in St. Louis
2009-2024
Tongde Hospital of Zhejiang Province
2023
Hope Center for Neurological Disorders
2013-2021
Yan'an University
2019
Shanghai Ninth People's Hospital
2017
Cedars-Sinai Medical Center
2014-2015
Significance It has been proposed that differential physical interactions of apolipoprotein E (apoE) isoforms with soluble amyloid-β (Aβ) in brain fluids influence the metabolism Aβ, providing a major mechanism to account for how APOE influences Alzheimer’s disease risk. The current study challenges this proposal and clearly shows lipoproteins containing apoE are unlikely play significant role Aβ by binding directly physiological such as cerebrospinal fluid or interstitial fluid. Our vitro...
ABCA1 is an ATP-binding cassette protein that transports cellular cholesterol and phospholipids onto high density lipoproteins (HDL) in plasma. Lack of humans mice causes abnormal lipidation increased catabolism HDL, resulting very low plasma apoA-I, apoA-II, HDL. Herein, we have used Abca1-/- to ask whether involved HDL the central nervous system (CNS). ApoE most abundant CNS apolipoprotein present HDL-like CSF. We found greatly decreased apoE levels both cortex (80% reduction) CSF (98%...
Although tau is a cytoplasmic protein, it also found in brain extracellular fluids, e.g., CSF. Recent findings suggest that aggregated can be transferred between cells and aggregates might mediate spread of pathology. Despite these data, details whether normally released into the interstitial fluid (ISF), its concentration ISF relation to CSF, influenced by aggregation are unknown. To address issues, we developed microdialysis technique analyze monomeric levels within hippocampus awake,...
Recent genome-wide association studies linked variants in TREM2 to a strong increase the odds of developing Alzheimer’s disease. The mechanism by which influences susceptibility disease is currently unknown. expressed microglia and thought regulate phagocytic inflammatory microglial responses brain pathology. Given that single allele variant TREM2, likely resulting loss function, conferred an increased risk disease, we tested whether one functional trem2 would affect Aβ plaque deposition or...
One of the hallmarks Alzheimer's disease is presence extracellular diffuse and fibrillar plaques predominantly consisting amyloid-β (Aβ) peptide. Apolipoprotein E (ApoE) influences deposition amyloid pathology through affecting clearance aggregation monomeric Aβ in brain. In addition to influencing metabolism, increasing evidence suggests that apoE microglial function neurodegenerative diseases. Here, we characterize impact has on innate immune response APPPS1ΔE9 APPPS1-21 transgenic mice....
Age-related aggregation of amyloid-β (Aβ) is an upstream pathological event in Alzheimer's disease (AD) pathogenesis, and it disrupts the sleep-wake cycle. The amount sleep declines with aging to a greater extent AD. Poor quality insufficient amounts have been noted humans preclinical evidence However, how affects Aβ not yet well understood. Orexins (hypocretins) initiate maintain wakefulness, loss orexin-producing neurons causes narcolepsy. We tried determine whether orexin release or...
Abstract Aggregated insoluble tau is one of two defining features Alzheimer’s disease. Because clinical symptoms are strongly correlated with aggregates, drug development and diagnosis need cost-effective accessible specific fluid biomarkers aggregates; however, recent studies suggest that the currently available cannot specifically track aggregates. We show microtubule-binding region (MTBR) containing residue 243 (MTBR-tau243) a new cerebrospinal (CSF) biomarker for aggregates compared it...
The ε4 allele of the apolipoprotein E (APOE) gene is strongest genetic risk factor for Alzheimer's disease (AD). Evidence suggests that effect apoE isoforms on amyloid-β (Aβ) accumulation in brain plays a critical role AD pathogenesis. Like humans, apoE4 expression animal models develop Aβ amyloidosis results greater and amyloid deposition than with apoE3 expression. However, whether decreasing levels or would promote attenuate Aβ-related pathology has not been directly addressed. To...
We previously found a strong reduction in tau pathology and insoluble P301S transgenic mice following intracerebroventricular infusion of the anti-tau antibody HJ8.5. sought to determine effects HJ8.5 same model peripheral administration.The primary objective was if administered at dose 50 mg kg(-1) week(-1) by intraperitoneal (IP) injection 6-month-old for 3 months would influence phospho-tau (p-tau) accumulation, insolubility, neurodegeneration.Treatment with mg/kg showed very decrease...
Cushing disease caused by adrenocorticotropin (ACTH)-secreting pituitary adenomas leads to hypercortisolemia predisposing diabetes, hypertension, osteoporosis, central obesity, cardiovascular morbidity, and increased mortality. There is no effective targeted pharmacotherapy for disease. Here, we generated germline transgenic zebrafish with overexpression of tumor transforming gene ( PTTG/securin ) the adenohypophyseal proopiomelanocortin (POMC) lineage, which recapitulated early features...
Abstract Background The APOE4 allele variant is the strongest known genetic risk factor for developing late-onset Alzheimer’s disease. link between apolipoprotein E (apoE) and disease likely due in large part to impact of apoE on metabolism amyloid β (Aβ) within brain. Manipulation levels lipidation brain has been proposed as a therapeutic target treatment However, we know little about dynamic regulation central nervous system. We have developed an assay measure interstitial fluid awake...
Apolipoprotein E (apoE) is the strongest known genetic risk factor for late onset Alzheimer's disease (AD). It influences amyloid-β (Aβ) clearance and aggregation, which likely contributes in large part to its role AD pathogenesis. We recently found that HJ6.3, a monoclonal antibody against apoE, significantly reduced Aβ plaque load when given APPswe/PS1ΔE9 (APP/PS1) mice starting before of deposition. To determine whether anti-apoE HJ6.3 affects plaques, neuronal network function, behavior...
Administration of an anti-tau antibody to transgenic mice expressing human tau and patients with tauopathy increased the concentration in plasma.
Context:Cushing disease, due to pituitary corticotroph tumor ACTH hypersecretion, drives excess adrenal cortisol production with adverse morbidity and mortality. Loss of glucocorticoid negative feedback on the hypothalamic-pituitary-adrenal axis leads autonomous transcription precursor hormone proopiomelanocortin (POMC), consequent overproduction, hypercortisolism. We previously reported that R-roscovitine (CYC202, seliciclib), a 2,6,9-trisubstituted purine analog, suppresses...
Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% young women. Mammals exposed elevated androgens in utero develop PCOS-like phenotypes adulthood, suggesting fetal origins PCOS. We hypothesize that androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism unexposed subsequent generations. Zebrafish were used study underlying mechanism origins. Embryos (testosterone dihydrotestosterone) at 26 56 hours...
Amyloid β (Aβ) accumulates in the extracellular space as diffuse and neuritic plaques Alzheimer's disease (AD). Aβ also deposits on walls of arterioles cerebral amyloid angiopathy (CAA) most cases AD sometimes independently AD. Apolipoprotein E (apoE) ɛ4 is associated with increases both CAA humans. Studies mouse models that develop deposition have shown murine apoE human apoE4 different abilities to facilitate plaque or formation when studied independently. To better understand compare...
Hyperinsulinemia is a risk factor for late-onset Alzheimer9s disease (AD). <i>In vitro</i> experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but <i>in vivo</i> are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving <i>APP<sub>swe</sub></i>/<i>PS1<sub>dE9</sub></i> transgenic mice. Both postprandial...
The risk of Alzheimer's disease (AD) is highly dependent on apolipoprotein-E (apoE) genotype. reasons for apoE isoform-selective are uncertain; however, both the amounts and structure human isoforms have been hypothesized to lead amyloidosis increasing AD. To address hypothesis that different in CNS, we developed a novel isoform-specific method accurately quantify clinically relevant samples. utilizes an antibody-free enrichment step isotope-labeled physiologically lipoprotein particle...
Azvudine and nirmatrelvir-ritonavir are more extensively used to treat COVID-19 in China due their earlier approval by the National Medical Products Administration. However, there has been a scarcity of research directly comparing clinical outcomes between azvudine till now. We aimed make head-to-head comparison efficacy safety or hospitalized patients with China. This retrospective cohort study was conducted using data collected from Tongde Hospital Zhejiang Province December 2022 January...
Current fetal alcohol spectrum disorders (FASD) studies primarily focus on alcohol's actions the brain although respiratory infections are a leading cause of morbidity/mortality in newborns. The limited examining pulmonary adaptations FASD demonstrate decreased surfactant protein A and alveolar macrophage phagocytosis, impaired differentiation, increased risk Group B streptococcal pneumonia with no study sexual dimorphism adaptations. We hypothesized that developmental exposure pregnancy...