Your search for: 'author:("Jia, Jianping")' has returned 47 results. (0.026s) Save search

Authors: Chen, Shuoqi | Jia, Jianping

Article Type: Research Article

Abstract: Background: Inflammation and oxidative stress are believed to play an important role in the pathogenesis of Alzheimer’s disease (AD). Tenuifolin (TEN) is a natural neuroprotective compound extracted from Polygala tenuifolia Willd , which may improve cognitive symptoms. Objective: This study was designed to evaluate the protective effect of TEN on inflammatory and oxidative stress induced by amyloid-β (Aβ)42 oligomers in BV2 cells, and to explore the underlying mechanisms. Methods: We conducted cell viability assays to estimate drug toxicity and drug effects on cells. Quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays were performed to detect the release of inflammatory …factors. Nitric oxide (NO) assays were used to measure the degree of oxidative stress. Western blot and immunofluorescence analysis were used to explore the influence of TEN on the nuclear factor-κ B (NF-κ B) pathway. Results: Pretreatment of BV2 microglial cells with TEN inhibited the release of tumor necrosis factor-α , interleukin-6, and interleukin-1β, alleviated NO-induced oxidative stress by inhibiting the expression of inducible nitric oxide synthase and cyclo-oxygenase-2, and protected SH-SY5Y cells from the toxicity induced by the medium conditioned by BV2 cells previously exposed to Aβ42 oligomers. Moreover, TEN suppressed upstream activators of NF-κ B, as well as NF-κ B translocation to the nucleus in BV2 microglial cells. Conclusion: This study demonstrates that TEN can protect SH-SY5Y cells from Aβ42 oligomer-induced microglia-mediated inflammation, and oxidative stress by downregulating the NF-κ B signaling pathway. Show more

Keywords: Alzheimer disease, amyloid-β protein, inflammation, nuclear factor-κB, microglia

DOI: 10.3233/JAD-200077

Citation: Journal of Alzheimer's Disease, vol. 76, no. 1, pp. 195-205, 2020

Authors: Zhang, Yue | Jia, Jianping

Article Type: Research Article

Abstract: Background: Microglia-driven neuroinflammation has been shown to be involved in the entire process of Alzheimer’s disease (AD). Betaine is a natural product that exhibits anti-inflammatory activity; however, the exact underlying molecular mechanisms are poorly understood. Objective: Our study focused on determining the effect of betaine against amyloid-β42 oligomer (AβO)-induced inflammation in microglial BV2 cells and investigating the underlying mechanism. Methods: AβO was used to establish an in vitro AD model using BV2 cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay was used to measure BV2 cell viability with different concentrations of AβO and betaine. Reverse transcription–polymerase chain reaction and enzyme-linked immunosorbent assays were …used to determine the expression levels of inflammatory factors, such as interleukin-1β (IL-1β), interleukin-18 (IL-18), and tumor necrosis factor α (TNF-α). Western blotting was used to evaluate the activation of the NOD-like receptor pyrin domain containing-3 (NLRP3) inflammasome and nuclear transcription factor-κB p65 (NF-κB p65). Moreover, we used phorbol 12-myristate 13-acetate (PMA) to activate NF-κB in order to validate that betaine exerted anti-neuroinflammatory effects through regulation of the NF-κB/NLRP3 signaling pathway. Results: We used 2 mM betaine to treat 5μM AβO-induced microglial inflammation. The administration of betaine effectively decreased the levels of IL-1β, IL-18, and TNF-α without affecting cell viability in BV2 microglial cells. Conclusion: Betaine inhibited AβO-induced neuroinflammation in microglia by inhibiting the activation of the NLRP3 inflammasome and NF-κB, which supports further evaluation of betaine as a potential effective modulator for AD. Show more

Keywords: Alzheimer’s disease, betaine, neuroinflammation, NF-κB, NLRP3

DOI: 10.3233/JAD-230064

Citation: Journal of Alzheimer's Disease, vol. 94, no. s1, pp. S9-S19, 2023

Authors: Xu, Hui | Jia, Jianping

Article Type: Research Article

Abstract: Background: The pathogenesis of Alzheimer’s disease (AD) involves various immune-related phenomena; however, the mechanisms underlying these immune phenomena and the potential hub genes involved therein are unclear. An understanding of AD-related immune hub genes and regulatory mechanisms would help develop new immunotherapeutic targets. Objective: The aim of this study was to explore the hub genes and the mechanisms underlying the regulation of competitive endogenous RNA (ceRNA) in immune-related phenomena in AD pathogenesis. Methods: We used the GSE48350 data set from the Gene Expression Omnibus database and identified AD immune-related differentially expressed RNAs (DERNAs). We constructed protein–protein interaction (PPI) networks for …differentially expressed mRNAs and determined the degree for screening hub genes. By determining Pearson’s correlation coefficient and using StarBase, DIANA-LncBase, and Human MicroRNA Disease Database (HMDD), the AD immune-related ceRNA network was generated. Furthermore, we assessed the upregulated and downregulated ceRNA subnetworks to identify key lncRNAs. Results: In total, 552 AD immune-related DERNAs were obtained. Twenty hub genes, including PIK3R1 , B2M , HLA-DPB1 , HLA-DQB1 , PIK3CA , APP , CDC42 , PPBP , C3AR1 , HRAS , PTAFR , RAB37 , FYN , PSMD1 , ACTR10 , HLA-E , ARRB2 , GGH , ALDOA , and VAMP2 were identified on PPI network analysis. Furthermore, upon microRNAs (miRNAs) inhibition, we identified LINC00836 and DCTN1-AS1 as key lncRNAs regulating the aforementioned hub genes. Conclusion: AD-related immune hub genes include B2M , FYN , PIK3R1 , and PIK3CA , and lncRNAs LINC00836 and DCTN1-AS1 potentially contribute to AD immune-related phenomena by regulating AD-related hub genes. Show more

Keywords: Alzheimer’s disease, competitive endogenous RNA, hub genes, immune system

DOI: 10.3233/JAD-200081

Citation: Journal of Alzheimer's Disease, vol. 77, no. 3, pp. 1255-1265, 2020

Authors: Zhao, Tan | Quan, Meina | Jia, Jianping

Article Type: Research Article

Abstract: Background: The default mode network (DMN) could be divided into subsystems, the functional connectivity of which are different across the Alzheimer’s disease (AD) spectrum. However, the functional connectivity patterns within the subsystems are unknown in presymptomatic autosomal dominant AD (ADAD). Objective: To investigate functional connectivity patterns within the subsystems of the DMN in presymptomatic subjects carrying PSEN1 , PSEN2 , or APP gene mutations. Methods: Twenty-six presymptomatic mutation carriers (PMC) and twenty-nine cognitively normal non-carriers as normal controls (NC) from the same families underwent resting state functional MRI and structural MRI. Seed-based analyses were done to obtain functional connectivity of …posterior and anterior DMN. For the regions that showed significant connectivity difference between PMC and NC, volumes were extracted and compared between the two groups. Connectivity measures were then correlated with cognitive tests scores. Results: The posterior DMN showed connectivity decrease in the PMC group as compared with the NC group, which was primarily the connectivity of left precuneus with right precuneus and superior frontal gyrus; the anterior DMN showed significant connectivity decrease in the PMC group, which was the connectivity of medial frontal gyrus with middle frontal gyrus. In the brain regions showing connectivity changes in the PMC group, there was no group difference in volume. A positive correlation was observed between the precuneus connectivity value and Mini-Mental State Examination total score. Conclusion: Functional connectivity within both posterior and anterior DMN were disrupted in the presymptomatic stage of ADAD. Connectivity disruption within the posterior DMN may be useful for early identification of general cognitive decline and a potential imaging biomarker for early diagnosis. Show more

Keywords: Autosomal dominant Alzheimer’s disease, default mode network, functional connectivity, structural imaging

DOI: 10.3233/JAD-191065

Citation: Journal of Alzheimer's Disease, vol. 73, no. 4, pp. 1435-1444, 2020

Authors: Li, Hanzhi | Jia, Jianping | Yang, Zhiqiang

Article Type: Research Article

Abstract: Background: Chinese nationwide norms of the Mini-Mental State Examination (MMSE) have not been established despite its wide use. Objective: To obtain norms for the MMSE based on age, gender, education, and rural or urban residences and to determine the optimal cut-off points of the MMSE in elderly Chinese. Methods: A cross-sectional study was conducted in Chinese community residents aged 65 years or over selected by cluster random sampling. The MMSE was administered to 9,629 subjects (7,110 cognitively normal, 2,024 with mild cognitive impairment, and 495 with dementia). The demographic influences on MMSE scores were investigated and the norms were established …considering those factors. Receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off points. Results: Years of education (standardized β= 0.399), rural residence (standardized β= –0.261), age (standardized β= –0.198), and being female (standardized β= –0.101) had significant effects on MMSE scores (p  < 0.001). Accordingly, we presented the demographic-stratified normative data for the MMSE. The optimal cut-off points for dementia screening were 16/17 for illiterate (sensitivity 87.6% and specificity 80.8%), 19/20 for individuals with 1–6 years of education (sensitivity 93.6% and specificity 92.7%), and 23/24 for individuals with 7 or more years of education (sensitivity 94.3% and specificity 94.3%). Conclusion: We provide the age-, gender-, education-, and residence-specific reference norms for the MMSE derived from an investigation of a large-scale, multicenter, nationwide representative Chinese elderly population. It could be of great improvement for the use of the MMSE in dementia screening in Chinese elderly population. Show more

Keywords: Dementia, elderly, mild cognitive impairment, Mini-Mental State Examination

DOI: 10.3233/JAD-160119

Citation: Journal of Alzheimer's Disease, vol. 53, no. 2, pp. 487-496, 2016

Authors: Zhu, Min | Jia, Longfei | Jia, Jianping

Article Type: Research Article

Abstract: Background: Imbalance between amyloid-β (Aβ) production and clearance results in Aβ accumulation. Regulating Aβ levels is still a hot point in the research of Alzheimer’s disease (AD). Objective: To identify the differential expression of ATP-binding cassette transporter A1 (ABCA1) and its upstream microRNA (miRNA) in AD models, and to explore their relationships with Aβ levels. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to determine the expression of ABCA1 in 5xFAD mice, SH-SY5Y cells treated with Aβ oligomers and SH-SY5YA βPP 695 cells (AD models). TargetScan was used to predict the upstream miRNAs for ABCA1. Dual-luciferase …assay was conducted to identify the regulation of the miRNA on ABCA1. qRT-PCR was used to measure the expression of miRNA in AD models. Finally, enzyme-linked immunosorbent assays were performed to detect Aβ42 and Aβ40 levels. Results: The expression of ABCA1 was significantly downregulated in AD models at both mRNA and protein levels. Dual-luciferase assay showed that miR-96-5p could regulate the expression of ABCA1 through binding to the 3 untranslated region of ABCA1. The level of miR-96-5p was significantly elevated in AD models. The expression of ABCA1 was enhanced while Aβ42 levels and Aβ42 /Aβ40 ratios were reduced in SH-SY5YA βPP 695 cells after treated with miR-96-5p inhibitor. Conclusion: The current study found that miR-96-5p is the upstream miRNA for ABCA1. Suppression of miR-96-5p in AD models could reduce Aβ42 /Aβ40 ratios via upregulating the expression of ABCA1, indicating that miR-96-5p plays an important role in regulating the content of Aβ. Show more

Keywords: Alzheimer’s disease, amyloid-β, ATP-binding cassette transporter A1, microRNA

DOI: 10.3233/JAD-210411

Citation: Journal of Alzheimer's Disease, vol. 83, no. 1, pp. 367-377, 2021

Authors: Yan, Xin | Li, Fangyu | Chen, Shuoqi | Jia, Jianping

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) exerts a heavy burden on China. Substantial factors are found associated with high expenditure of AD in high-income countries. To date, few studies have been conducted in China. Objective: This study aimed to analyze the associated factors of the total annual costs of AD in China. Methods: Data were drawn from a multi-center, cross-sectional, socioeconomic study on the costs of AD conducted in China from October 2015 to March 2016. Generalized linear model (GLM) using gamma distribution with a log-link function was employed to examine the associated factors of the total cost. Results: Univariate analysis showed …that the demographic and clinical characteristics of AD patients and their caregivers had a substantial impact on the total cost. In GLM analysis, age, monthly household income, AD severity, number of comorbidities, and treatment with memantine were associated with higher expenditure, while the use of a nursing home/care facility was associated with lower expenditure. The mean annual costs for patients with severe dementia were almost twice as high as those for patients with mild dementia (US$ 25,601 versus US$ 13,387, p  < 0.001). The mean total cost of AD patients with at least five comorbidities (US$ 38,348) was almost three times than those with no comorbidities (US$ 13,744). Conclusion: In China, AD severity and comorbidities were the most critical factors impacting the total cost. Optimizing care patterns, delaying disease progression, and managing comorbidities comprehensively could decrease the heavy burden of AD. Show more

Keywords: Alzheimer’s disease, caregiver, cost of illness, comorbidity, dementia severity

DOI: 10.3233/JAD-190166

Citation: Journal of Alzheimer's Disease, vol. 69, no. 3, pp. 795-806, 2019

Authors: Li, Fangyu | Qin, Wei | Zhu, Min | Jia, Jianping

Article Type: Research Article

Abstract: Background: Current and future incidence and prevalence estimates of dementia are essential for public health planning. Objective: The objective was to establish prediction model of incidence and estimate the prevalence of dementia in the Chinese and worldwide population from 2020 to 2050. Methods: A model-based method was used to project the dementia prevalence from 2020 to 2050 in China, which required incidence, the mortality rate for individual without dementia, and the relative risk of death. Furthermore, we detected the impact of intervention on the prevalence projection for dementia using a simulation method. We applied the same method to other projections …worldwide. Results: In 2020, the model predicted 16.25 million (95%confidence interval 11.55–21.18) persons with dementia in China. By 2050, this number would increase by approximately three-fold to 48.98 million (38.02–61.73). Through data simulation, if the incidence of dementia decreased by 10%every 10 years from 2020 after intervention and prevention, the number of dementia cases by 2050 was reduced by 11.96 million. This would reduce the economic burden by US $639.04 billion. In addition, using this model, dementia cases grew relatively slowly over the next few decades in the United States of America, the United Kingdom, and Japan, with percentage changes of 100.88%, 65.93%, and 16.20%, respectively. Conclusion: The number of people with dementia in China is large and will continue to increase rapidly. Effective interventions could reduce the number of patients drastically. Therefore, prevention and control strategies must be formulated urgently to reduce the occurrence of dementia. Show more

Keywords: China, dementia, model-based, prevalence, projection

DOI: 10.3233/JAD-210493

Citation: Journal of Alzheimer's Disease, vol. 82, no. 4, pp. 1823-1831, 2021

Authors: Song, Yang | Quan, Meina | Li, Tingting | Jia, Jianping

Article Type: Research Article

Abstract: Background: Although elevated levels of homocysteine (Hcy) are associated with cognitive impairment and dementia, the relevance of Hcy, vitamin B12 , and folate levels to subtypes of dementia are still unknown. Objective: To investigate the changes of Hcy, vitamin B12 , and folate levels in mild cognitive impairment (MCI) and subtypes of dementia including Alzheimer’s disease (AD), vascular dementia (VaD), frontotemporal dementia (FTD), and Lewy body dementia (LBD), and their relationships with cognitive function and magnetic resonance imaging (MRI) markers. Methods: We measured serum levels of Hcy, vitamin B12 , and folate in 257 subjects. Each subject underwent cognitive function …assessment and brain MRI test. The Fazekas and temporal lobe atrophy (MTA) visual rating scales were used to assess the degree of white matter hyperintensities and MTA, respectively. Results: Serum levels of Hcy was higher and vitamin B12 was lower in AD, VaD, FTD, and LBD groups than cognitively normal controls. No significant differences of folate levels were found among 6 groups. Hcy levels were positively correlated with MTA total score in AD (r  = 0.448, p  < 0.001). Vitamin B12 levels were positively correlated with MoCA in VaD (r  = 0.497), and negatively correlated with MTA total score in AD (r  = – 0.325) (p s < 0.05). Hyperhomocysteinemia may increase the risk of AD (OR = 2.744), VaD (OR = 3.600), and FTD (OR = 3.244) in the adjusted model (p s < 0.05). Conclusion: Hcy and vitamin B12 levels are associated with MTA in AD. Vitamin B12 levels are associated with general cognition in VaD. Hyperhomocysteinemia is a risk factor for not only AD and VaD but also FTD. Show more

Keywords: Alzheimer’s disease, B vitamin, dementia, frontotemporal dementia, homocysteine, Lewy body dementia, mild cognitive impairment, vascular dementia

DOI: 10.3233/JAD-220410

Citation: Journal of Alzheimer's Disease, vol. 90, no. 2, pp. 681-691, 2022

Authors: Wang, Wei | Wei, Cuibai | Quan, Meina | Li, Tingting | Jia, Jianping

Article Type: Research Article

Abstract: Background: Depression is one of the most common behavioral and psychological symptoms in people with Alzheimer’s disease (AD). To date, however, the molecular mechanisms underlying the clinical association between depression and AD remained elusive. Objective: Here, we study the relationship between memory impairment and depressive-like behavior in AD animal model, and investigate the potential mechanisms. Methods: Male SD rats were administered amyloid-β oligomers (AβOs) by intracerebroventricular injection, and then the depressive-like behavior, neuroinflammation, oxidative stress, and the serotonergic system were measured in the brain. Sulforaphane (SF), a compound with dual capacities of anti-inflammation and anti-oxidative stress, was injected intraperitoneally to …evaluate the therapeutic effect. Results: The results showed that AβOs induced both memory impairment and depressive-like behavior in rats, through the mechanisms of inducing neuroinflammation and oxidative stress, and impairing the serotonergic axis. SF could reduce both inflammatory factors and oxidative stress parameters to protect the serotonergic system and alleviate memory impairment and depressive-like behavior in rats. Conclusion: These results provided insights into the biological mechanisms underlying the clinical link between depressive disorder and AD, and offered new drug options for the treatment of depressive symptoms in dementia. Show more

Keywords: Alzheimer’s disease, amyloid-β oligomers, depression, neuroinflammation, oxidative stress, sulforaphane

DOI: 10.3233/JAD-200397

Citation: Journal of Alzheimer's Disease, vol. 78, no. 1, pp. 127-137, 2020