Yi Li
Profile Url: yi-li
Researcher at Institute of Hydrobiology, Chinese Academy of Sciences
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Translational Psychiatry, 2018-04-11
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Translational Psychiatry
Neurodegenerative diseases likely share common underlying pathobiology. Although prior work has identified susceptibility loci associated with various dementias, few, if any, studies have systematically evaluated shared genetic risk across several neurodegenerative diseases. Using genome-wide association data from large studies (total n = 82,337 cases and controls), we utilized a previously validated approach to identify genetic overlap and reveal common pathways between progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), Parkinson's disease (PD) and Alzheimer's disease (AD). In addition to the MAPT H1 haplotype, we identified a variant near the chemokine receptor CXCR4 that was jointly associated with increased risk for PSP and PD. Using bioinformatics tools, we found strong physical interactions between CXCR4 and four microglia related genes, namely CXCL12, TLR2, RALB and CCR5. Evaluating gene expression from post-mortem brain tissue, we found that expression of CXCR4 and microglial genes functionally related to CXCR4 was dysregulated across a number of neurodegenerative diseases. Furthermore, in a mouse model of tauopathy, expression of CXCR4 and functionally associated genes was significantly altered in regions of the mouse brain that accumulate neurofibrillary tangles most robustly. Beyond MAPT, we show dysregulation of CXCR4 expression in PSP, PD, and FTD brains, and mouse models of tau pathology. Our multi-modal findings suggest that abnormal signaling across a network of microglial genes may contribute to neurodegeneration and may have potential implications for clinical trials targeting immune dysfunction in patients with neurodegenerative diseases.
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BackgroundRecent studies have reported numerous significant predictors for adverse outcomes in COVID-19 disease. However, there have been few simple clinical risk score for prompt risk stratification. The objective is to develop a simple risk score for severe COVID-19 disease using territory-wide healthcare data based on simple clinical and laboratory variables. MethodsConsecutive patients admitted to Hong Kongs public hospitals between 1st January and 22nd August 2020 diagnosed with COVID-19, as confirmed by RT-PCR, were included. The primary outcome was composite intensive care unit admission, need for intubation or death with follow-up until 8th September 2020. ResultsCOVID-19 testing was performed in 237493 patients and 4445 patients (median age 44.8 years old, 95% CI: [28.9, 60.8]); 50% male) were tested positive. Of these, 212 patients (4.8%) met the primary outcome. A risk score including the following components was derived from Cox regression: gender, age, hypertension, stroke, diabetes mellitus, ischemic heart disease/heart failure, respiratory disease, renal disease, increases in neutrophil count, monocyte count, sodium, potassium, urea, alanine transaminase, alkaline phosphatase, high sensitive troponin-I, prothrombin time, activated partial thromboplastin time, D-dimer and C-reactive protein, as well as decreases in lymphocyte count, base excess and bicarbonate levels. The model based on test results taken on the day of admission demonstrated an excellent predictive value. Incorporation of test results on successive time points did not further improve risk prediction. ConclusionsA simple clinical score accurately predicted severe COVID-19 disease, even without including symptoms, blood pressure or oxygen status on presentation, or chest radiograph results.