27 results on '"Tang, Beisha"'
Search Results
2. Identification of CHCHD10 Mutation in Chinese Patients with Alzheimer Disease
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Xiao, Tingting, Jiao, Bin, Zhang, Weiwei, Pan, Chuzheng, Wei, Jingya, Liu, Xiaoyan, Zhou, Yafang, Zhou, Lin, Tang, Beisha, and Shen, Lu
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- 2017
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3. Machine learning based on Optical Coherence Tomography images as a diagnostic tool for Alzheimer's disease.
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Wang, Xin, Jiao, Bin, Liu, Hui, Wang, Yaqin, Hao, Xiaoli, Zhu, Yuan, Xu, Bei, Xu, Huizhuo, Zhang, Sizhe, Jia, Xiaoliang, Xu, Qian, Liao, Xinxin, Zhou, Yafang, Jiang, Hong, Wang, Junling, Guo, Jifeng, Yan, Xinxiang, Tang, Beisha, Zhao, Rongchang, and Shen, Lu
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OPTICAL coherence tomography ,ALZHEIMER'S disease ,MACHINE learning ,DIAGNOSTIC imaging ,MONTREAL Cognitive Assessment ,VISUAL fields ,MILD cognitive impairment - Abstract
Aims: We mainly evaluate retinal alterations in Alzheimer's disease (AD) patients, investigate the associations between retinal changes with AD biomarkers, and explore an optimal machine learning (ML) model for AD diagnosis based on retinal thickness. Methods: A total of 159 AD patients and 299 healthy controls were enrolled. The retinal parameters of each participant were measured using optical coherence tomography (OCT). Additionally, cognitive impairment severity, brain atrophy, and cerebrospinal fluid (CSF) biomarkers were measured in AD patients. Results: AD patients demonstrated a significant decrease in the average, superior, and inferior quadrant peripapillary retinal nerve fiber layer, macular retinal nerve fiber layer, ganglion cell layer (GCL), inner plexiform layer (IPL) thicknesses, as well as total macular volume (TMV) (all p < 0.05). Moreover, TMV was positively associated with Mini‐Mental State Examination and Montreal Cognitive Assessment scores, IPL thickness was correlated negatively with the medial temporal lobe atrophy score, and the GCL thickness was positively correlated with CSF Aβ42/Aβ40 and negatively associated with p‐tau level. Based on the significantly decreased OCT variables between both groups, the XGBoost algorithm exhibited the best diagnostic performance for AD, whose four references, including accuracy, area under the curve, f1 score, and recall, ranged from 0.69 to 0.74. Moreover, the macular retinal thickness exhibited an absolute superiority for AD diagnosis compared with other enrolled variables in all ML models. Conclusion: We identified the retinal alterations in AD patients and found that macular thickness and volume were associated with AD severity and biomarkers. Furthermore, we confirmed that OCT combined with ML could serve as a potential diagnostic tool for AD. [ABSTRACT FROM AUTHOR]
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- 2022
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4. Macular Microvascular Density as a Diagnostic Biomarker for Alzheimer's Disease.
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Wang, Xin, Wang, Yaqin, Liu, Hui, Zhu, Xiangyu, Hao, Xiaoli, Zhu, Yuan, Xu, Bei, Zhang, Sizhe, Jia, Xiaoliang, Weng, Ling, Liao, Xinxin, Zhou, Yafang, Tang, Beisha, Zhao, Rongchang, Jiao, Bin, and Shen, Lu
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Background: Some previous studies showed abnormal pathological and vascular changes in the retina of patients with Alzheimer's disease (AD). However, whether retinal microvascular density is a diagnostic indicator for AD remains unclear.Objective: This study evaluated the macular vessel density (m-VD) in the superficial capillary plexus and fovea avascular zone (FAZ) area in AD, explored their correlations with clinical parameters, and finally confirmed an optimal machine learning model for AD diagnosis.Methods: 77 patients with AD and 145 healthy controls (HCs) were enrolled. The m-VD and the FAZ area were measured using optical coherence tomography angiography (OCTA) in all participants. Additionally, AD underwent neuropsychological assessment, brain magnetic resonance imaging scan, cerebrospinal fluid (CSF) biomarker detection, and APOE ɛ4 genotyping. Finally, the performance of machine learning algorithms based on the OCTA measurements was evaluated by Python programming language.Results: The m-VD was noticeably decreased in AD compared with HCs. Moreover, m-VD in the fovea, superior inner, inferior inner, nasal inner subfields, and the whole inner ring declined significantly in mild AD, while it was more serious in moderate/severe AD. However, no significant difference in the FAZ was noted between AD and HCs. Furthermore, we found that m-VD exhibited a significant correlation with cognitive function, medial temporal atrophy and Fazekas scores, and APOE ɛ4 genotypes. No significant correlations were observed between m-VD and CSF biomarkers. Furthermore, results revealed the Adaptive boosting algorithm exhibited the best diagnostic performance for AD.Conclusion: Macular vascular density could serve as a diagnostic biomarker for AD. [ABSTRACT FROM AUTHOR]- Published
- 2022
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5. CYLD variants identified in Alzheimer's disease and frontotemporal dementia patients.
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Xiao, Xuewen, Xu, Tianyan, Liu, Hui, Liu, Xixi, Liao, Xinxin, Zhou, Yafang, Zhou, Lu, Wang, Xin, Zhu, Yuan, Yang, Qijie, Hao, Xiaoli, Liu, Yingzi, Jiang, Hong, Guo, Jifeng, Wang, Junling, Tang, Beisha, Li, Jinchen, Shen, Lu, and Jiao, Bin
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ALZHEIMER'S disease ,FRONTOTEMPORAL dementia ,DEMENTIA patients ,AMYOTROPHIC lateral sclerosis ,APOLIPOPROTEIN E4 ,CHINESE people - Abstract
Objectives: CYLD was a novel causative gene for frontotemporal dementia (FTD) and amyotrophic lateral sclerosis. Given the clinical and pathological overlap of FTD and Alzheimer's disease (AD), it is necessary to screen CYLD in AD patients and FTD patients in the Chinese population. Methods: In our study, using a targeted sequencing panel, we sequenced the CYLD gene in a large cohort of 2485 participants in the Chinese population, including 1008 AD patients, 105 FTD patients, and 1372 controls. Results: In the present study, the average onset age of AD and FTD patients was 66.84 ± 30.42 years old and 60 ± 10.00 years old, respectively. Our study reported three novel CYLD variants: p.Phe288Leu (patient No. 1, AD), p.Tyr485Phe (patients No. 6–9, all AD) and p.Thr951Ala (patient No. 10, AD), plus a previously reported variant: p.Arg397Ser (patient No. 2–5, AD and No. 11, FTD). These variants were absent in our in‐house controls and predicted to be deleterious according to the MutationTaster. The variant carriers were composed of 10 AD patients and one FTD patient, and the average onset age was 61.2 ± 10.9 years. The frequency of CYLD variants in AD was similar to that in FTD, which was 0.99% (10/1008) and 0.95% (1/105), respectively. Interpretation: Our finding extended the genotype and phenotype of the CYLD gene and demonstrated that CYLD rare damaging variants may be implicated in AD and FTD pathogenesis. [ABSTRACT FROM AUTHOR]
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- 2022
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6. Performance of Plasma Amyloid β, Total Tau, and Neurofilament Light Chain in the Identification of Probable Alzheimer's Disease in South China.
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Jiao, Bin, Liu, Hui, Guo, Lina, Liao, Xinxin, Zhou, Yafang, Weng, Ling, Xiao, Xuewen, Zhou, Lu, Wang, Xin, Jiang, Yaling, Yang, Qijie, Zhu, Yuan, Zhou, Lin, Zhang, Weiwei, Wang, Junling, Yan, Xinxiang, Tang, Beisha, and Shen, Lu
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TAU proteins ,APOLIPOPROTEIN E ,ALZHEIMER'S disease ,CYTOPLASMIC filaments ,AMYLOID ,COGNITIVE ability - Abstract
Background: Alzheimer's disease (AD) is the most common type of dementia and has no effective treatment to date. It is essential to develop a minimally invasive blood-based biomarker as a tool for screening the general population, but the efficacy remains controversial. This cross-sectional study aimed to evaluate the ability of plasma biomarkers, including amyloid β (Aβ), total tau (t-tau), and neurofilament light chain (NfL), to detect probable AD in the South Chinese population. Methods: A total of 277 patients with a clinical diagnosis of probable AD and 153 healthy controls with normal cognitive function (CN) were enrolled in this study. The levels of plasma Aβ42, Aβ40, t-tau, and NfL were detected using ultra-sensitive immune-based assays (SIMOA). Lumbar puncture was conducted in 89 patients with AD to detect Aβ42, Aβ40, t-tau, and phosphorylated (p)-tau levels in the cerebrospinal fluid (CSF) and to evaluate the consistency between plasma and CSF biomarkers through correlation analysis. Finally, the diagnostic value of plasma biomarkers was further assessed by constructing a receiver operating characteristic (ROC) curve. Results: After adjusting for age, sex, and the apolipoprotein E (APOE) alleles, compared to the CN group, the plasma t-tau, and NfL were significantly increased in the AD group (p < 0.01, Bonferroni correction). Correlation analysis showed that only the plasma t-tau level was positively correlated with the CSF t-tau levels (r = 0.319, p = 0.003). The diagnostic model combining plasma t-tau and NfL levels, and age, sex, and APOE alleles, showed the best performance for the identification of probable AD [area under the curve (AUC) = 0.89, sensitivity = 82.31%, specificity = 83.66%]. Conclusion: Blood biomarkers can effectively distinguish patients with probable AD from controls and may be a non-invasive and efficient method for AD pre-screening. [ABSTRACT FROM AUTHOR]
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- 2021
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7. p38 MAPK‐mediated loss of nuclear RNase III enzyme Drosha underlies amyloid beta‐induced neuronal stress in Alzheimer's disease.
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Xu, Haidong, Liu, Xiaolei, Li, Wenming, Xi, Ye, Su, Peng, Meng, Bo, Shao, Xiaoyun, Tang, Beisha, Yang, Qian, and Mao, Zixu
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ALZHEIMER'S disease ,AMYLOID ,LABORATORY rats ,MICRORNA ,AMYLOID beta-protein ,NON-coding RNA ,ANIMAL disease models ,PROTEIN fractionation - Abstract
MicroRNAs (miRNAs) are small noncoding RNAs ubiquitously expressed in the brain and regulate gene expression at the post‐transcriptional level. The nuclear RNase III enzyme Drosha initiates the maturation process of miRNAs in the nucleus. Strong evidence suggests that dysregulation of miRNAs is involved in many neurological disorders including Alzheimer's disease (AD). Dysfunction of miRNA biogenesis components may be involved in the processes of those diseases. However, the role of Drosha in AD remains unknown. By using immunohistochemistry, biochemistry, and subcellular fractionation methods, we show here that the level of Drosha protein was significantly lower in the postmortem brain of human AD patients as well as in the transgenic rat model of AD. Interestingly, Drosha level was specifically reduced in neurons of the cortex and hippocampus but not in the cerebellum in the AD brain samples. In primary cortical neurons, amyloid‐beta (Aβ) oligomers caused a p38 MAPK‐dependent phosphorylation of Drosha, leading to its redistribution from the nucleus to the cytoplasm and a decrease in its level. This loss of Drosha function preceded Aβ‐induced neuronal death. Importantly, inhibition of p38 MAPK activity or overexpression of Drosha protected neurons from Aβ oligomers‐induced apoptosis. Taken together, these results establish a role for p38 MAPK‐Drosha pathway in modulating neuronal viability under Aβ oligomers stress condition and implicate loss of Drosha as a key molecular change in the pathogenesis of AD. [ABSTRACT FROM AUTHOR]
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- 2021
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8. METTL3-dependent RNA m6A dysregulation contributes to neurodegeneration in Alzheimer's disease through aberrant cell cycle events.
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Zhao, Fanpeng, Xu, Ying, Gao, Shichao, Qin, Lixia, Austria, Quillan, Siedlak, Sandra L., Pajdzik, Kinga, Dai, Qing, He, Chuan, Wang, Wenzhang, O'Donnell, James M., Tang, Beisha, and Zhu, Xiongwei
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CELL cycle ,ALZHEIMER'S disease ,RNA metabolism ,RNA modification & restriction ,COGNITION disorders ,NEURODEGENERATION ,HIPPOCAMPUS (Brain) - Abstract
Background: N6-methyladenosine (m
6 A) modification of RNA influences fundamental aspects of RNA metabolism and m6 A dysregulation is implicated in various human diseases. In this study, we explored the potential role of RNA m6 A modification in the pathogenesis of Alzheimer disease (AD). Methods: We investigated the m6 A modification and the expression of m6 A regulators in the brain tissues of AD patients and determined the impact and underlying mechanism of manipulated expression of m6 A levels on AD-related deficits both in vitro and in vivo. Results: We found decreased neuronal m6 A levels along with significantly reduced expression of m6 A methyltransferase like 3 (METTL3) in AD brains. Interestingly, reduced neuronal m6 A modification in the hippocampus caused by METTL3 knockdown led to significant memory deficits, accompanied by extensive synaptic loss and neuronal death along with multiple AD-related cellular alterations including oxidative stress and aberrant cell cycle events in vivo. Inhibition of oxidative stress or cell cycle alleviated shMettl3-induced apoptotic activation and neuronal damage in primary neurons. Restored m6 A modification by inhibiting its demethylation in vitro rescued abnormal cell cycle events, neuronal deficits and death induced by METTL3 knockdown. Soluble Aβ oligomers caused reduced METTL3 expression and METTL3 knockdown exacerbated while METTL3 overexpression rescued Aβ-induced synaptic PSD95 loss in vitro. Importantly, METTL3 overexpression rescued Aβ-induced synaptic damage and cognitive impairment in vivo. Conclusions: Collectively, these data suggested that METTL3 reduction-mediated m6 A dysregulation likely contributes to neurodegeneration in AD which may be a therapeutic target for AD. [ABSTRACT FROM AUTHOR]- Published
- 2021
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9. The role of NOTCH3 variants in Alzheimer's disease and subcortical vascular dementia in the Chinese population.
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Guo, Lina, Jiao, Bin, Liao, Xinxin, Xiao, Xuewen, Zhang, Weiwei, Yuan, Zhenhua, Liu, Xixi, Zhou, Lu, Wang, Xin, Zhu, Yuan, Yang, Qijie, Wang, Junling, Tang, Beisha, and Shen, Lu
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ALZHEIMER'S disease ,CHINESE people ,VASCULAR dementia ,VASCULAR diseases ,LEUKOENCEPHALOPATHIES ,DEMENTIA patients - Abstract
Aims: NOTCH3 gene mutations predominantly cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, a common etiology of subcortical vascular dementia (SVaD). Besides, there may be a pathogenic link between NOTCH3 variants and Alzheimer's disease (AD). We aimed to study the role of NOTCH3 variants in AD and SVaD patients. Methods: We recruited 763 patients with dementia (667 AD and 96 SVaD) and 365 healthy controls from the Southern Han Chinese population. Targeted capture sequencing was performed on NOTCH3 coding and adjacent intron regions to detect the pathogenic variants in AD and SVaD. The relationship between common or rare NOTCH3 variants and AD was further analyzed using Plink1.9. Results: Five known pathogenic variants (p.R182C, p.C201S, p.R544C, p.R607C, and p.R1006C) and two novel likely pathogenic variants (p.C201F and p.C1061F) were detected in 16 SVaD patients. Additionally, no pathogenic or likely pathogenic variants were found in AD patients. NOTCH3 was not associated with AD in either single‐variant association analysis or gene‐based association analysis. Conclusion: Our findings broaden the mutational spectrum of NOTCH3 and validate the pathogenic role of NOTCH3 mutations in SVaD, but do not support the notion that NOTCH3 variation influences the risk of AD. [ABSTRACT FROM AUTHOR]
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- 2021
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10. Preliminary Study of hsa-mir-626 Change in the Cerebrospinal Fluid in Parkinson's Disease.
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Qin, Li-Xia, Tan, Jie-Qiong, Zhang, Hai-Nan, Tang, Jian-Guang, Jiang, Bo, Shen, Xiang-Min, Guo, Ji-Feng, Tan, Li-Ming, Tang, Beisha, and Wang, Chun-Yu
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PARKINSON'S disease ,CEREBROSPINAL fluid ,CENTRAL nervous system diseases ,DRUG target ,ALZHEIMER'S disease ,ENCEPHALITIS ,MOVEMENT disorders ,SELF-monitoring (Psychology) ,RNA - Abstract
Context: A host of microRNAs have been reported to suppress tumor growth, invasion, and metastasis and play roles in neurodegeneration disorders. Moreover, microRNA changes are found in the peripheral blood, cerebrospinal fluid (CSF), and brain tissues of central nervous system diseases, including glioma, Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis, and depression. Compared with other body fluids, CSF can reflect the brain pathological processes more accurately.Aims: To understand whether microRNA expression may be misregulated in patients with PD, and further discover potential diagnostic biomarkers and promising therapeutic targets for PD.Materials and Methods: Here, through real-time reverse-transcription polymerase chain reaction (RT-PCR), we compared CSF microRNA from 15 PD patients, 11 AD patients, and 16 controls with other neurologic disorders, such as encephalitis and Guillain-Barre syndrome.Results: Finally, we identified hsa-miR-626 changes in the CSF of PD patients. The mean expression level of hsa-miR-626 was significantly reduced in the CSF of PD patients compared with AD patients and controls.Conclusions: Our approach provides a preliminary research for identifying biomarkers in the CSF that could be used for the detection, diagnosis, and monitoring of PD. [ABSTRACT FROM AUTHOR]- Published
- 2021
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11. Association of Genes Involved in the Metabolic Pathways of Amyloid-β and Tau Proteins With Sporadic Late-Onset Alzheimer's Disease in the Southern Han Chinese Population.
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Xiao, Xuewen, Jiao, Bin, Liao, Xinxin, Zhang, Weiwei, Yuan, Zhenhua, Guo, Lina, Wang, Xin, Zhou, Lu, Liu, Xixi, Yan, Xinxiang, Tang, Beisha, and Shen, Lu
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CHINESE people ,TAU proteins ,ALZHEIMER'S disease ,SINGLE nucleotide polymorphisms ,GENES - Abstract
The genes involved in the metabolic pathways of amyloid-β (Aβ) and tau proteins significantly influence the etiology of Alzheimer's disease (AD). Various studies have explored the associations between some of these genes and AD in the Caucasian population; however, researches regarding these associations remain limited in the Chinese population. To systematically evaluate the associations of these genes with AD, we investigated 19 genes involved in the metabolism of Aβ and tau based on previous studies selected using the PubMed database. This study included 372 patients with sporadic late-onset AD (sLOAD) and 345 cognitively healthy individuals from southern China. The results were replicated in the International Genomics of Alzheimer's Project (IGAP). Protein–protein interactions were determined using the STRING v11 database. We found that a single-nucleotide polymorphism, rs11682128, of BIN1 conferred susceptibility to sLOAD after adjusting for age, sex, and APOE ε4 status and performing the Bonferroni correction {corrected P = 0.000153, odds ratio (OR) [95% confidence interval (CI)] = 1.403 (1.079–1.824)}, which was replicated in the IGAP. Protein–protein interactions indicated that BIN1 was correlated with MAPT. Moreover, rare variants of NEP and FERMT2 (0.0026 < corrected P < 0.05), and the Aβ degradation, tau pathology, and tau phosphatase pathways (0.01 < corrected P < 0.05), were nominally significantly associated with sLOAD. This study suggested that the genes involved in the metabolic pathways of Aβ and tau contributed to the etiology of sLOAD in the southern Han Chinese population. [ABSTRACT FROM AUTHOR]
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- 2020
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12. Association of rare variants in neurodegenerative genes with familial Alzheimer's disease.
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Zhang, Weiwei, Jiao, Bin, Xiao, Tingting, Liu, Xixi, Liao, Xinxin, Xiao, Xuewen, Guo, Lina, Yuan, Zhenhua, Yan, Xinxiang, Tang, Beisha, and Shen, Lu
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ALZHEIMER'S disease ,PARKINSON'S disease ,GENETIC mutation ,EAST Asians ,GENES - Abstract
Objective: To investigate the impact of rare variants underlying neurodegenerative‐related genes to familial Alzheimer's disease (AD). Methods: We performed targeted sequencing of 277 neurodegenerative‐related genes on probands from 75 Chinese AD families non‐carrying causative mutation of dementia genes. Rare coding variants segregated in families were tested for association in an independent cohort of 506 patients with sporadic AD and 498 cognitively normal controls. East Asians data from the Exome Aggregation Consortium (ExAC) were used as a reference control. Results: A novel rare variant, P410S of PLD3 was found in an early‐onset AD family. LRRK2 I2012T, a causative mutation of Parkinson's disease, was identified in another early‐onset AD family. Missense variants in ABCA7 (P143S and A1507T) and CR1(T239M) were significantly associated with familial AD (P = 0.005437, 0.001383, 0.000549), a missense variant in TREM2(S183C) was significantly associated with AD (P = 0.000396) when compared with the East Asian controls in ExAC database. A non‐frameshift variant in FUS (G223del) was frequent in AD cases and significantly associated with familial AD (P = 0.008). Interpretation: Multiple rare coding variants of causal and risk neurodegenerative genes were presented in clinically diagnosed AD families that may confer risk of AD. Our data supported that the clinical, pathological, and genetic architectures of AD, PD, and FTD/ALS may overlapping. We propose that targeted sequencing on neurodegenerative‐related genes is necessary for genetically unclear AD families. [ABSTRACT FROM AUTHOR]
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- 2020
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13. The sterol regulatory element‐binding protein 2 is dysregulated by tau alterations in Alzheimer disease.
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Wang, Chunyu, Zhao, Fanpeng, Shen, Katie, Wang, Wenzhang, Siedlak, Sandra L., Lee, Hyoung‐gon, Phelix, Clyde F., Perry, George, Shen, Lu, Tang, Beisha, Yan, Riqiang, and Zhu, Xiongwei
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STEROL regulatory element-binding proteins ,NEUROFIBRILLARY tangles ,ALZHEIMER'S disease ,PYRAMIDAL neurons - Abstract
Disturbed neuronal cholesterol homeostasis has been observed in Alzheimer disease (AD) and contributes to the pathogenesis of AD. As the master switch of cholesterol biosynthesis, the sterol regulatory element‐binding protein 2 (SREBP‐2) translocates to the nucleus after cleavage/activation, but its expression and activation have not been studied in AD which is the focus of the current study. We found both a significant decrease in the nuclear translocation of N‐terminal SREBP‐2 accompanied by a significant accumulation of C‐terminal SREBP‐2 in NFT‐containing pyramidal neurons in AD. N‐terminal‐ SREBP‐2 is also found in dystrophic neurites around plaques in AD brain. Western blot confirmed a significantly reduced nuclear translocation of mature SREBP‐2 (mSREBP‐2) in AD brain. Interestingly, reduced nuclear mSREBP‐2 was only found in animal models of tauopathies such as 3XTg AD mice and P301L Tau Tg mice but not in CRND8 APP transgenic mice, suggesting that tau alterations likely are involved in the changes of mSREBP‐2 distribution and activation in AD. Altogether, our study demonstrated disturbed SREBP‐2 signaling in AD and related models, and proved for the first time that tau alterations contribute to disturbed cholesterol homeostasis in AD likely through modulation of nuclear mSREBP‐2 translocation. [ABSTRACT FROM AUTHOR]
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- 2019
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14. MicroRNAs in Alzheimer's Disease.
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Wang, Mengli, Qin, Lixia, and Tang, Beisha
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MICRORNA ,ALZHEIMER'S disease ,DEMENTIA ,MEMORY loss ,MILD cognitive impairment ,ALZHEIMER'S patients ,NEUROFIBRILLARY tangles - Abstract
Alzheimer's disease (AD) is a progressive and devastating neurodegenerative disorder. It is the leading cause of dementia in the world's rapidly growing aging population. The characteristics of AD are memory loss and cognitive impairment, meaning patients cannot carry out their daily activities independently. The increase of AD cases poses heavy burdens on families, society and the economy. Despite frequent efforts being made to research the etiology of AD, the causes of AD remain unknown, and no curative treatments are available yet. The pathological hallmarks of AD are amyloid plaques and neurofibrillary tangles in the brain. MicroRNAs are endogenous ∼22 nucleotides non-coding RNAs that could regulate gene expression at a post-transcriptional level by transcript degradation or translation repression. MicroRNAs are involved in many biological processes and diseases, particularly multifactorial diseases, providing an excellent tool with which to research the mechanisms of these diseases. AD is a multifactorial disorder, and accumulating evidence shows that microRNAs play a critical role in the pathogenesis of AD. In this review, we will highlight the effect of microRNAs in different pathological processes throughout AD progression. [ABSTRACT FROM AUTHOR]
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- 2019
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15. Multiple Visual Rating Scales Based on Structural MRI and a Novel Prediction Model Combining Visual Rating Scales and Age Stratification in the Diagnosis of Alzheimer's Disease in the Chinese Population.
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Yuan, Zhenhua, Pan, Chuzheng, Xiao, Tingting, Liu, Menghui, Zhang, Weiwei, Jiao, Bin, Yan, Xinxiang, Tang, Beisha, and Shen, Lu
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MAGNETIC resonance imaging ,VISUAL analytics ,ALZHEIMER'S disease ,CHINESE people ,SENSITIVITY analysis - Abstract
Objective: To explore the value of multiple visual rating scales based on structural MRI in the diagnosis of Alzheimer's disease (AD) in the Chinese population. Materials and Methods: One hundred patients with AD and 100 age- and gender- matched cognitively normal controls were enrolled in this study. All the participants underwent neuropsychological tests and a structural MRI scan of the brain, among them, 42 AD cases and 47 cognitively normal controls also underwent 3D-T1 weighted sequence used for the analysis of voxel-based morphometry (VBM). The AD cases were divided into mild and moderate–severe groups according to the mini-mental state examination. Each participant was evaluated by two trained radiologists who were blind to the clinical information, according to the six visual rating scales, including for medial temporal lobe atrophy (MTA), posterior atrophy (PA), anterior temporal (AT), orbitofrontal (OF) cortex, anterior cingulate (AC), and fronto-insula (FI). Finally, we estimated the relationship between the visual rating scales and the volume of corresponding brain regions, using correlation analysis, and evaluated the specificity and sensitivity of every single scale and combination of multiple scales in the diagnosis of AD, using a receiver operating characteristic (ROC) curve and establishing a logistic regression model. Results: The optimal cutoff of all six visual rating scales for distinguishing AD cases from normal controls was 1.5. Using automated classification based on all six rating scales, the accuracy for distinguishing AD cases from healthy controls ranged from 0.68 to 0.80 (for mild AD) and 0.77–0.90 (for moderate–severe AD), respectively. A diagnostic prediction model with a combination of MTA and OF results was made as follows: Score = B
MTA(score) + BOF(score) −1.58 (age < 65 years); Score = BMTA(score) + BOF(score) −4.09 (age ≥65 years). The model was superior to any single visual rating scale in the diagnosis of mild AD (P < 0.05). Conclusion: Each of the six visual rating scales could be applied to the diagnosis of moderate-severe AD alone in the Chinese population. A prediction model of the combined usage of MTA, OF, and age stratification for the early diagnosis of AD was preliminarily established. [ABSTRACT FROM AUTHOR]- Published
- 2019
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16. Identification of CHCHD2 mutations in patients with Alzheimer's disease, amyotrophic lateral sclerosis and frontotemporal dementia in China.
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Liu, Xixi, Jiao, Bin, Zhang, Weiwei, Xiao, Tingting, Hou, Lihua, Pan, Chuzheng, Tang, Beisha, and Shen, Lu
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ALZHEIMER'S disease ,AMYOTROPHIC lateral sclerosis ,FRONTOTEMPORAL dementia ,EXONS (Genetics) ,PARKINSON'S disease - Abstract
Recently, the coiled-coil-helix-coiled-coil-helix domain 2 (CHCHD2) gene was identified as a possible causative gene for Parkinson's disease (PD). Three other neurodegenerative diseases, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), share significant overlaps with PD in clinical phenotypes, pathological features and genetic heredities, and it is still unclear whether CHCHD2 variants could explain these three diseases. The present study screened all exons of the CHCHD2 gene in a total of 780 patients (511 AD, 181 ALS and 88 FTD) and 500 healthy controls from the Chinese Han population. Two missense variants, 5C>T (Pro2Leu) and 238A>G (Ile80Val), were identified in five unrelated patients with AD while no mutations were observed in patients with ALS or FTD. These mutations have been reported as low-frequency variants in the ExAC database with frequencies of 0.0075 and 0.000025. Pro2 Leu, however, was also detected in controls and was confirmed to have no significant association with the risk for AD; Ile80Val was not detected in any normal controls, suggesting that the CHCHD2 gene may be associated with AD in the Chinese Han population. [ABSTRACT FROM AUTHOR]
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- 2018
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17. Identification of rare <italic>RTN3</italic> variants in Alzheimer’s disease in Han Chinese.
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Zou, Yongyi, He, Wanxia, Wang, Kangli, Han, Hailong, Xiao, Tingting, Chen, Xumeng, Zhou, Bin, Tan, Jieqiong, Xia, Kun, Tang, Beisha, Chen, Chao, Shen, Lu, Yan, Riqiang, and Zhang, Zhuohua
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RETICULON proteins ,ALZHEIMER'S disease ,AMYLOID beta-protein precursor ,LUCIFERASE genetics ,PROTEOLYTIC enzymes - Abstract
Reticulon 3 (RTN3) is a neuronally-expressed reticulon family protein that was previously shown to negatively regulate BACE1, a protease that is required for the generation of β-amyloid peptides (Aβ) from amyloid precursor protein. Despite biochemical and morphological evidence that supports a role of RTN3 in the formation of neuritic amyloid plaques, no systematic analyses of
RTN3 mutations in patients with Alzheimer’s disease (AD) have yet been reported.RTN3 were targeted sequenced in 154 sporadic early-onset and 285 late-onset AD patients. Luciferase reporter assay and kymographs were performed to analysis the expression of RNT3 and BACE1-RFP particle mobility on cells transfected with wild-type or variants RTN3 constructs. We identified heterozygous variants such as c.-8G > T, c.17C > A, c.42C > T, and c.116C > T from patients in the early-onset AD group and c.-8G > T, c.17C > A, from patients in the late-onset AD group. Such variants of RTN3 were not observed in control individuals. Further biochemical studies show that theRTN3 c.-8G > T variant in the 5′-untranslated region appears to cause reduced expression of RTN3. TheRTN3 c.116 C > T variant causes a change of codon T39 to M39 (T39 M). Overexpression of RTN3 T39 M in cultured neurons led to impaired axonal transport of BACE1. The variants found in this study are likely genetic modifiers for RTN3-mediated formation of neuritic plaques in AD. [ABSTRACT FROM AUTHOR]- Published
- 2018
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18. Alzheimer's Disease: From Genetic Variants to the Distinct Pathological Mechanisms.
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Qiying Sun, Xie, Nina, Tang, Beisha, Li, Rena, and Yong Shen
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ALZHEIMER'S disease ,NEURODEGENERATION ,MOLECULAR diagnosis - Abstract
Being the most common cause of dementia, AD is a polygenic and neurodegenerative disease. Complex and multiple factors have been shown to be involved in its pathogenesis, of which the genetics play an indispensable role. It is widely accepted that discovery of potential genes related to the pathogenesis of AD would be of great help for the understanding of neurodegeneration and thus further promote molecular diagnosis in clinic settings. Generally, AD could be clarified into two types according to the onset age, the early-onset AD (EOAD) and the late-onset AD (LOAD). Progresses made by genetic studies on both EOAD and LOAD are believed to be essential not only for the revolution of conventional ideas but also for the revelation of new pathological mechanisms underlying AD pathogenesis. Currently, albeit the genetics of LOAD is much less well-understood compared to EOAD due to its complicated and multifactorial essence, Genome-wide association studies (GWASs) and next generation sequencing (NGS) approaches have identified dozens of novel genes that may provide insight mechanism of LOAD. In this review, we analyze functions of the genes and summarize the distinct pathological mechanisms of how these genes would be involved in the pathogenesis of AD. [ABSTRACT FROM AUTHOR]
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- 2017
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19. Effect of the CYP2D6 and APOE Polymorphisms on the Efficacy of Donepezil in Patients with Alzheimer's Disease: A Systematic Review and Meta-Analysis.
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Xiao, Tingting, Jiao, Bin, Zhang, Weiwei, Tang, Beisha, and Shen, Lu
- Subjects
CYTOCHROME P-450 CYP2D6 ,DRUG efficacy ,DONEPEZIL ,ALZHEIMER'S disease treatment ,NEURODEGENERATION ,THERAPEUTICS ,HYDROCARBONS ,NOOTROPIC agents ,PIPERIDINE ,ALZHEIMER'S disease ,ANIMAL experimentation ,APOLIPOPROTEINS ,GENETIC polymorphisms ,META-analysis ,OXIDOREDUCTASES ,PHARMACOGENOMICS ,SYSTEMATIC reviews - Abstract
Background: Differential responses to donepezil treatment in patients with Alzheimer's disease (AD) have been observed in clinical practice. It remains controversial whether, and to what extent, individual variation in the genes responsible for drug metabolism (CYP2D6) or those associated with AD pathogenesis (APOE) modulate the response to donepezil treatment.Objective: The aim of this study was to better understand the potential link between donepezil treatment response and CYP2D6 or APOE polymorphisms.Methods: We performed a meta-analysis based on data collected from 1266 donepezil-treated AD patients, and evaluated the association of CYP2D6 or APOE polymorphisms with treatment effectiveness.Results: No significant difference was observed in the responder rate of donepezil treatment between the normal function CYP2D6 alleles group and the decreased/non-functional group [odds ratio (OR) 1.34, 95 % confidence interval (CI) 0.5-3.58; p = 0.56]. However, compared with the increased function CYP2D6 alleles group, the normal function group had a better response to donepezil treatment (OR 1.52, 95 % CI 1.14-2.03; p = 0.005). For the specific CYP2D6 single nucleotide polymorphism rs1080985, patients who carried the G allele had a significantly higher risk of poor response to donepezil treatment. After adjusting the data based on APOE genotype, it was observed that only individuals bearing both the APOE-ε4 allele and the rs1080985-G allele showed a significant increase in the frequency of treatment non-response (OR 1.73, 95 % CI 1.07-2.09; p = 0.03). No independent effect of APOE polymorphism on donepezil clinical responses was found (OR 1.08, 95 % CI 0.85-1.38; p = 0.53). Lastly, in a subgroup analysis based on ethnicity, all results remained consistent.Conclusion: The CYP2D6 genotype may be potentially effective for predicting the response to donepezil treatment in AD patients. [ABSTRACT FROM AUTHOR]- Published
- 2016
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20. Increased Plasma TACE Activity in Subjects with Mild Cognitive Impairment and Patients with Alzheimer's Disease.
- Author
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Sun, Qiying, Hampel, Harald, Blennow, Kaj, Lista, Simone, Levey, Allan, Tang, Beisha, Li, Rena, and Shen, Yong
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MILD cognitive impairment ,ALZHEIMER'S disease research ,TUMOR necrosis factor receptors ,TUMOR necrosis factor converting enzyme ,CEREBROSPINAL fluid ,BLOOD plasma - Abstract
Evidence suggests that the tumor necrosis factor receptor (TNFR)-signaling pathway contributes to the pathogenesis of Alzheimer's disease (AD). TNF-α converting enzyme (TACE/ADAM-17) can cleave both pro-TNF-α and TNF receptors. Recently, we have shown that TACE activity in the cerebrospinal fluid (CSF) of subjects with mild cognitive impairment (MCI) and AD patients is significantly higher than that of cognitively healthy controls (HC). To date, it is not clear whether TACE activity could be detected in the human plasma and whether TACE activity in MCI and AD patients is different from that in HC. We analyzed TACE expression and activity in a large clinical sample of 64 patients with AD, 88 subjects with MCI, and 50 age-matched HC recruited from two distinct academic centers. Plasma TACE protein levels did not differ significantly in the three study groups (AD, MCI, and HC). However, plasma TACE activity in subjects with MCI and AD patients was significantly higher than that in HC. Moreover, in MCI and AD groups, we found a significant correlation between plasma TACE activity and CSF t-tau and Aβ42 levels and CSF Aβ42/tau ratios. In AD patients, the levels of plasma TACE activity correlated significantly and negatively with cognition. These findings further support the role of the TNF-α receptor complex in AD-related neuroinflammation and propose TACE plasma activity as a promising hypothesis-driven biomarker candidate for detection, diagnosis, and prognosis of prodromal and clinical AD. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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21. Specific serum autoantibodies predict the development and progression of Alzheimer's disease with high accuracy.
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Fang, Liangjuan, Jiao, Bin, Liu, Xixi, Wang, Zhenghong, Yuan, Peng, Zhou, Hui, Xiao, Xuewen, Cao, Liqin, Guo, Jifeng, Tang, Beisha, and Shen, Lu
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ALZHEIMER'S disease , *AUTOANTIBODIES , *TAU proteins , *CEREBROSPINAL fluid , *MILD cognitive impairment , *AUTOIMMUNE diseases , *CEREBRAL amyloid angiopathy - Abstract
• AD onset and progression were accompanied with an unappreciated serum autoantibody response. • Seven candidate serum AD-specific autoantibodies were identified. • A combinatory signature of the seven autoantibodies showed high accuracy in distinguishing AD. • The autoantibody alternation provide an opportunity to identify patients with MCI. Autoimmunity plays a key role in the pathogenesis of Alzheimer's disease (AD). However, whether autoantibodies in peripheral blood can be used as biomarkers for AD has been elusive. Serum samples were obtained from 1,686 participants, including 767 with AD, 146 with mild cognitive impairment (MCI), 255 with other neurodegenerative diseases, and 518 healthy controls. Specific autoantibodies were measured using a custom-made immunoassay. Multivariate support vector machine models were employed to investigate the correlation between serum autoantibody levels and disease states. As a result, seven candidate AD-specific autoantibodies were identified, including MAPT, DNAJC8, KDM4D, SERF1A, CDKN1A, AGER, and ASXL1. A classification model with high accuracy (area under the curve (AUC) = 0.94) was established. Importantly, these autoantibodies could distinguish AD from other neurodegenerative diseases and out-performed amyloid and tau protein concentrations in cerebrospinal fluid in predicting cognitive decline (P < 0.001). This study indicated that AD onset and progression are possibly accompanied by an unappreciated serum autoantibody response. Therefore, future studies could optimize its application as a convenient biomarker for the early detection of AD. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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22. Mutational analysis in early-onset familial Alzheimer's disease in Mainland China.
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Jiao, Bin, Tang, Beisha, Liu, Xiaoyan, Xu, Jun, Wang, Yanjiang, Zhou, Lin, Zhang, Fufeng, Yan, Xinxiang, Zhou, Yafang, and Shen, Lu
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ALZHEIMER'S disease , *GENETIC mutation , *PRESENILINS , *PHENOTYPES , *NUCLEOTIDE sequence - Abstract
Abstract: Mutations of 3 causative genes, namely presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP), have been identified as the major causes of early-onset familial Alzheimer's disease (EOFAD). Recently, a GGGGCC repeat expansion in the noncoding region of C9orf72 was also detected in some patients with clinically diagnosed familial Alzheimer's disease. The prevalence of causative gene mutations in patients with EOFAD has been reported in previous studies but their prevalence remains unclear in Mainland China. The aim of this study was to characterize the common causative gene mutation spectrum and genotype-phenotype correlations in Chinese patients with EOFAD. Genetic screening for mutations in PSEN1, PSEN2, and APP was conducted in a total of 32 families with clinical diagnoses of EOFAD from Mainland China. Subsequently, a hexanucleotide repeat expansion in C9orf72 was detected in all patients. Four novel mutations in PSEN1 (p.A434T, p.I167del, p.F105C, and p.L248P) were identified in 4 respective families, and 1 previously recognized pathogenic mutation in APP (p.V717I) was detected in another 2 unrelated families. The PSEN2 mutation and pathogenic repeat expansions of C9orf72 were not detected in all patients. To the best of our knowledge, this is the first cohort report of a causative gene screen in patients with EOFAD in Mainland China. The analysis of the genetic-clinical correlations in this cohort supports the idea that the clinical phenotype might be influenced by specific genetic defects. [Copyright &y& Elsevier]
- Published
- 2014
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23. Evaluation of common and rare variants of Alzheimer's disease-causal genes in Parkinson's disease.
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Zeng, Qian, Pan, Hongxu, Zhao, Yuwen, Wang, Yige, Xu, Qian, Tan, Jieqiong, Yan, Xinxiang, Li, Jinchen, Tang, Beisha, and Guo, Jifeng
- Abstract
Introduction: Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common neurodegenerative diseases in the elderly. Recently, some variants of AD-causal genes (APP, PSEN1, PSEN2) have been reported in PD. In this study, we investigated the association between coding variants of AD-causal genes and PD in a large Chinese population cohort.Methods: We performed whole-exome sequencing (WES) on 1,917 patients with early-onset or familial PD and 1,652 controls, and whole-genome sequencing (WGS) on 1,962 sporadic late-onset PD and 1,279 controls. Genetic and phenotypic data were analyzed with regression analyses and the optimized sequence kernel association test. Further validation study was performed by Fisher's exact test.Results: We found that rs75733498 in the PSEN2 gene was significantly associated with early-onset or familial PD; however, no significant relationship was discovered between rs75733498 and sporadic late-onset PD. The result of the validation study still revealed a significant association between rs75733498 and PD. We observed a suggestive association with APP gene in early-onset or familial PD when considering damaging missense variants alone (p = 0.018) or combined with loss-of-function variants (p = 0.029). Further phenotypic analysis did not demonstrate any significant associations.Conclusion: Our results support a possible genetic contribution of AD-causal genes to PD. These findings warrant further genetic and functional confirmation, and more powerful association studies will better decipher the mechanisms of PD. [ABSTRACT FROM AUTHOR]- Published
- 2022
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24. Absence of coding somatic single nucleotide variants within well-known candidate genes in late-onset sporadic Alzheimer's Disease based on the analysis of multi-omics data.
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Min, Shishi, Li, Zongchang, Shieh, Annie, Giase, Gina, Bao, Riyue, Zhang, Chunling, Kuney, Liz, Kopp, Richard, Asif, Huma, Alliey-Rodriguez, Ney, Qin, Lixia, Craig, David Wesley, Faulkner, Geoffrey J., Gershon, Elliot S., Tang, Beisha, Chen, Chao, and Liu, Chunyu
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SINGLE nucleotide polymorphisms , *SOMATIC mutation , *ALZHEIMER'S disease , *DISEASE risk factors , *NUCLEOTIDE sequencing , *DATA analysis - Abstract
Somatic mutations arise randomly or are induced by environmental factors, which may increase the risk of Alzheimer's disease (AD). Identifying somatic mutations in sporadic AD (SAD) may provide new insight of the disease. To evaluate the potential contribution of somatic single nucleotide variations (SNVs), particularly that of well-known AD-candidate genes, we investigated sequencing data sets from four platforms: whole-genome sequencing (WGS), deep whole-exome sequencing (WES) on paired brain and liver samples, RNA sequencing (RNA-seq), and single-cell whole-genome sequencing (scWGS) of brain samples from 16 AD patients and 16 non-AD individuals. We found that the average number, mean variant allele fractions (VAFs) and mutational signatures of somatic SNVs have similar distributions between AD brains and non-AD brains. We did not identify any somatic SNVs within coding regions of the APP, PSEN1, PSEN2 , nor in APOE. This study shows that somatic SNVs within the coding region of AD-candidate genes are unlikely to be a common causal factor for SAD. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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25. MicroRNA-26a/Death-Associated Protein Kinase 1 Signaling Induces Synucleinopathy and Dopaminergic Neuron Degeneration in Parkinson's Disease.
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Su, Ying, Deng, Man-Fei, Xiong, Wan, Xie, Ao-Ji, Guo, Jifeng, Liang, Zhi-Hou, Hu, Bo, Chen, Jian-Guo, Zhu, Xiongwei, Man, Heng-Ye, Lu, Youming, Liu, Dan, Tang, Beisha, and Zhu, Ling-Qiang
- Subjects
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DOPAMINERGIC neurons , *PARKINSON'S disease , *PROTEIN kinases , *NEURODEGENERATION , *FLUORESCENCE in situ hybridization , *ALZHEIMER'S disease - Abstract
Abstract Background Death-associated protein kinase 1 (DAPK1) is a widely distributed serine/threonine kinase that is critical for cell death in multiple neurological disorders, including Alzheimer's disease and stroke. However, little is known about the role of DAPK1 in the pathogenesis of Parkinson's disease (PD), the second most common neurodegenerative disorder. Methods We used Western blot and immunohistochemistry to evaluate the alteration of DAPK1. Quantitative polymerase chain reaction and fluorescence in situ hybridization were used to analyze the expression of microRNAs in PD mice and patients with PD. Rotarod, open field, and pole tests were used to evaluate the locomotor ability. Immunofluorescence, Western blot, and filter traps were used to evaluate synucleinopathy in PD mice. Results We found that DAPK1 is posttranscriptionally upregulated by a reduction in microRNA-26a (miR-26a) caused by a loss of the transcription factor CCAAT enhancer-binding protein alpha. The overexpression of DAPK1 in PD mice is positively correlated with neuronal synucleinopathy. Suppressing miR-26a or upregulating DAPK1 results in synucleinopathy, dopaminergic neuron cell death, and motor disabilities in wild-type mice. In contrast, genetic deletion of DAPK1 in dopaminergic neurons by crossing DAT-Cre mice with DAPK1 floxed mice effectively rescues the abnormalities in mice with chronic MPTP treatment. We further showed that DAPK1 overexpression promotes PD-like phenotypes by direct phosphorylation of α-synuclein at the serine 129 site. Correspondingly, a cell-permeable competing peptide that blocks the phosphorylation of α-synuclein prevents motor disorders, synucleinopathy, and dopaminergic neuron loss in the MPTP mice. Conclusions miR-26a/DAPK1 signaling cascades are essential in the formation of the molecular and cellular pathologies in PD. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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26. Association between polymorphism of COMT gene (Val158Met) with Alzheimer's disease: An updated analysis.
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Yan, Weiqian, Zhao, Cheng, Sun, Lu, and Tang, Beisha
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GENETICS of Alzheimer's disease , *GENETIC polymorphisms , *METHYLTRANSFERASES , *NEURODEGENERATION , *DISEASE susceptibility , *META-analysis - Abstract
Previous studies have proposed the association between catechol-o-methyltransferase (COMT) Val158Met polymorphism and the risk of Alzheimer's disease (AD). However, there has been no solid conclusion from those reports because of the limited sample size and/or racial diversity. Here we aimed to give an in-depth and accurate evaluation of this association by performing a comprehensive literature search on websites including PubMed, EMBASE, Alzgene database, Cochrane library and Ovid database. In further meta-analysis we identified 10 case–control studies which contained total 2777 cases and 2829 controls. Summarized odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were assessed to reveal the association. There was no significant association between COMT Val158Met polymorphism and AD susceptibility in all genetic models for the entire population. In the contrast the subgroup analysis stratified by ethnicity revealed significant differences in the Asian population in the dominant (OR = 0.66, 95%CI = 0.50, 0.87, p = 0.004); homozygous (OR = 0.66, 95%CI = 0.50, 0.89, p = 0.006); and heterozygous models (OR = 0.65, 95%CI = 0.48, 0.87, p = 0.004). However, no association was found in the Caucasians population. Similarly to the overall analysis, subgroup analysis of the control population stratified with HWE showed negative results. With the latest comprehensive searching strategy, our updated meta-analysis suggested that COMT Val158Met polymorphism could decrease the risk of AD in the Asian population, but not in the Caucasian or the overall population. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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27. Rare, pathogenic variants in LRP10 are associated with amyotrophic lateral sclerosis in patients from mainland China.
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Ni, Jie, Liu, Zhen, Li, Wanzhen, Yuan, Yanchun, Huang, Ling, Hu, Yiting, Liu, Pan, Hou, Xiaorong, Jiao, Bin, Li, Jinchen, Shen, Lu, Jiang, Hong, Tang, Beisha, and Wang, Junling
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AMYOTROPHIC lateral sclerosis , *FRONTOTEMPORAL lobar degeneration , *PARKINSON'S disease , *APOLIPOPROTEIN E4 , *ALZHEIMER'S disease , *NEURODEGENERATION - Abstract
Low-density lipoprotein receptor-related protein 10 (LRP10) is associated with a series of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease which share genetic risk factors and pathophysiological processes with amyotrophic lateral sclerosis (ALS). To investigate whether LRP10 variants could cause a predisposition to ALS, we screened rare, pathogenic LRP10 variants among a cohort of 584 patients with ALS from mainland China and performed burden analysis using data from a large external database. A total of 7 rare, pathogenic variants in LRP10 , of which one (c.1182A>T, p.R394S) was novel, were identified in 11 unrelated patients. Burden analysis revealed significant associations between ALS and LRP10 at both the gene and single-variant levels (c.1721G>A, p.R574Q; c.1182A>T, p.R394S; and c.1681C>T, p.R561C). Interestingly, patients with sporadic ALS carrying variant c.1721G>A tended to have a bulbar onset, increased phenotype severity, and a worse prognosis. Our findings first provide independent evidence that rare, pathogenic LRP10 variants may be risk factors for ALS and delineate a special phenotype in patients with sporadic ALS carrying variant c.1721G>A. • For the first time, LRP10 variations are described in patients with amyotrophic lateral sclerosis (ALS) from mainland China. • Rare, pathogenic variants in LRP10 may be risk factors for ALS. • Patients with sporadic ALS carrying variant c.1721G>A tend to have a special phenotype. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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