Journal of Alzheimer's Disease最新文献_第5页

Modeling Alzheimer's disease: Bayesian copula graphical model from demographic, cognitive, and neuroimaging data. 阿尔茨海默病建模：从人口统计学、认知学和神经影像学数据中建立贝叶斯联结图模型。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-05-04 DOI: 10.1177/13872877251337944

Lucas Vogels, Reza Mohammadi, Marit Schoonhoven, Ş Ilker Birbil, Martin Dyrba

{"title":"Modeling Alzheimer's disease: Bayesian copula graphical model from demographic, cognitive, and neuroimaging data.","authors":"Lucas Vogels, Reza Mohammadi, Marit Schoonhoven, Ş Ilker Birbil, Martin Dyrba","doi":"10.1177/13872877251337944","DOIUrl":"https://doi.org/10.1177/13872877251337944","url":null,"abstract":"BackgroundThe early detection of Alzheimer's disease (AD) requires an understanding of the relationships between a wide range of features. Conditional independencies and partial correlations are suitable measures for these relationships, because they can identify the effects of confounding and mediating variables.ObjectiveTo estimate conditional dependencies and partial correlations between relevant features in AD using a Bayesian approach to Gaussian copula graphical models (GCGMs). This approach has two key advantages. First, it includes binary, discrete, and continuous variables. Second, it quantifies the uncertainty of the estimates. Despite these advantages, Bayesian GCGMs have not been applied to AD research yet.MethodsWe design a GCGM to find the conditional dependencies and partial correlations among brain-region specific gray matter volume and glucose uptake, amyloid-beta levels, demographic information, and cognitive test scores. We applied our model to <math><mn>1</mn><mspace></mspace><mn>022</mn></math> participants, including healthy and cognitively impaired, across different stages of AD.ResultsWe found that aging reduces cognition through three indirect pathways: hippocampal volume loss, posterior cingulate cortex (PCC) volume loss, and amyloid-beta accumulation. We found a positive partial correlation between being woman and cognition, but also discovered four indirect pathways that dampen this association in women: lower hippocampal volume, lower PCC volume, more amyloid-beta accumulation, and less education. We found limited relations between brain-region specific glucose uptake and cognition, but discovered that the hippocampus and PCC volumes are related to cognition.ConclusionsThis study shows that the use of GCGMs offers valuable insights into AD pathogenesis.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251337944"},"PeriodicalIF":3.4,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quantitatively assessing daily functional impairment in dementia by imaging cerebrovascular correlates. 通过脑血管相关成像定量评估痴呆患者的日常功能损害。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-05-02 DOI: 10.1177/13872877251333086

Min-Chien Tu, Ya-Kuei Yu, Hsiao-Wen Chung, Yen-Hsuan Hsu, Jir-Jei Yang, Wen-Chau Wu

{"title":"Quantitatively assessing daily functional impairment in dementia by imaging cerebrovascular correlates.","authors":"Min-Chien Tu, Ya-Kuei Yu, Hsiao-Wen Chung, Yen-Hsuan Hsu, Jir-Jei Yang, Wen-Chau Wu","doi":"10.1177/13872877251333086","DOIUrl":"https://doi.org/10.1177/13872877251333086","url":null,"abstract":"BackgroundImpaired daily functioning can change day-to-day activities at the early stage of dementia, in varied association with cognitive decline and/or affective symptoms. Current clinical practice uses scales to assess daily functioning and can be prone to subject/proxy-related bias.ObjectiveTo investigate the yet unclear cerebrovascular correlate of daily activities and the usefulness of cerebral blood flow (CBF) as a quantitative marker of functional impairment.MethodsNinety patients with clinically diagnosed dementia and 30 healthy controls were prospectively recruited. Regional CBF within the frontotemporal-subcortical circuits was quantified by magnetic resonance imaging, compared between control and CBF-stratified patient groups, and then correlated with basic and instrumental activities of daily living.ResultsLower CBF was found to associate with impaired daily activities in most of the regions investigated after adjusted for the effect of age and Mini-Mental State Examination score. Analyses of partial correlation and receiver operating characteristic further revealed that impaired basic activities of daily living was best detected by the baseline CBF in the right middle temporal gyrus, with the area under the curve (AUC) = 0.860 (p < 0.001). Impaired instrumental activities of daily living was best detected by the CBF in the right superior temporal gyrus (AUC = 0.695, p < 0.001). The CBF in the two regions showed no significant detecting ability for anxiety and depression.ConclusionsWe identified the cerebrovascular correlates of daily functioning in line with the previously conceptualized role of frontotemporal-subcortical circuits, allowing quantitative assessment of daily activities with minimal confounding from affective symptoms.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251333086"},"PeriodicalIF":3.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identifying the mediating role of brain atrophy on the relationship between DNA damage repair pathway and Alzheimer's disease: A Mendelian randomization analysis and mediation analysis. 确定脑萎缩在DNA损伤修复途径与阿尔茨海默病关系中的中介作用：孟德尔随机化分析和中介分析

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-05-02 DOI: 10.1177/13872877251333811

Wei Bao, Haidi Bi, Lishuo Chao, Yaqing Jiang, Xiaoping Yu, Fei Ruan, Di Wu, Zhaoyan Chen, Kai Le

{"title":"Identifying the mediating role of brain atrophy on the relationship between DNA damage repair pathway and Alzheimer's disease: A Mendelian randomization analysis and mediation analysis.","authors":"Wei Bao, Haidi Bi, Lishuo Chao, Yaqing Jiang, Xiaoping Yu, Fei Ruan, Di Wu, Zhaoyan Chen, Kai Le","doi":"10.1177/13872877251333811","DOIUrl":"https://doi.org/10.1177/13872877251333811","url":null,"abstract":"BackgroundDNA damage and repair (DDR) and structural atrophies in different brain regions were recognized as critical factors in the onset of Alzheimer's disease (AD).ObjectiveWe utilized Mendelian randomization (MR) to examine the causal effects of the DDR-related molecular traits on AD and the potential mediating roles of different brain region volumes.MethodsIn primary analysis, we utilized public genome-wide association studies of AD and summary data from existing molecular traits datasets, including gene expression, DNA methylation, and protein levels quantitative trait loci (eQTL, mQTL, and pQTL) in both blood and brain to examine their causal associations by summary-data-based MR analysis and additional five two-sample MR methods. Subsequently, mediation analysis explored the potential mediate roles of 13 imaging-derived brain volume phenotypes in the associations between the DDR pathways and AD through a network MR design.ResultsWe found that the volumes of the right thalamus proper and global cerebral white matter mediated the causal pathways from EGFR to AD and relatively weak mediation effects of the right lateral ventricle volume in the causal pathways involving CHRNE, DNTT, and AD.ConclusionsWe identified causal relationships among DDR pathways, specific brain region volumes, and AD. Monitoring the molecular traits of these DDR-related genes and developing targeted drugs may help detect and interrupt the early progression of AD.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251333811"},"PeriodicalIF":3.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TMA-93 (binding by images): Cutoffs optimization based on Alzheimer's disease biomarkers. TMA-93（图像结合）：基于阿尔茨海默病生物标志物的截断优化。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-05-01 Epub Date: 2025-03-21 DOI: 10.1177/13872877251325759

José Enrique Arriola-Infante, Ernesto García-Roldán, David García-Solís, Alba Marta Marín-Cabañas, Andrea Luque-Tirado, Ángela Almodóvar-Sierra, María Bernal Sánchez-Arjona, Didier Maillet, Emilio Franco-Macías

{"title":"TMA-93 (binding by images): Cutoffs optimization based on Alzheimer's disease biomarkers.","authors":"José Enrique Arriola-Infante, Ernesto García-Roldán, David García-Solís, Alba Marta Marín-Cabañas, Andrea Luque-Tirado, Ángela Almodóvar-Sierra, María Bernal Sánchez-Arjona, Didier Maillet, Emilio Franco-Macías","doi":"10.1177/13872877251325759","DOIUrl":"10.1177/13872877251325759","url":null,"abstract":"BackgroundWith the arrival of new disease-modifying treatments for Alzheimer's disease (AD), feasible cognitive tests, also for illiterate patients, are needed to screen those requiring deeper evaluation among individuals presenting with memory complaints. The TMA-93, a brief binding memory test, has proven useful for diagnosing early AD, and is supported by normative data that accounts for age and cognitive reserve.ObjectiveTo compare the sensitivity of different TMA-93 cutoffs in detecting AD pathology.MethodsA retrospective analysis was performed on a biobank sample of patients with confirmed AD pathology via amyloid PET or cerebrospinal fluid (CSF) biomarkers. The sensitivity of six TMA-93 cutoffs was evaluated: the 10th, 15th, and 20th percentiles based on traditional norming (TN) and regression-based norming (RBN). False negatives (FN) characteristics were also analyzed.ResultsA total of 270 AD-positive patients (96 by amyloid-PET, 174 by CSF biomarkers) were included, comprising 224 with mild cognitive impairment and 46 with mild dementia. The 15th percentile using RBN demonstrated substantial sensitivity (80.4%), higher than that of the 10th percentile, and also provided a more uniform distribution across normative groups compared to the TN approach. Higher global cognition (Mini-Mental State Examination score) and, in patients over 70, lower cognitive reserve (Cognitive Reserve Questionnaire), were linked to a greater likelihood of FN results.ConclusionsThe 15th percentile cutoff based on RBN, accounting for age and cognitive reserve, improves sensitivity for detecting AD pathology, making it a valuable screening tool for memory complaints. Future normative data from biomarker-negative subjects may enhance the sensitivity of cognitive tests.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"65-76"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identifying microglia-derived NFKBIA as a potential contributor to the pathogenesis of Alzheimer's disease and age-related macular degeneration. 确定小胶质细胞衍生的NFKBIA是阿尔茨海默病和年龄相关性黄斑变性发病机制的潜在贡献者。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-05-01 Epub Date: 2025-03-19 DOI: 10.1177/13872877251326267

Shizhen Lei, Yani Liu

{"title":"Identifying microglia-derived NFKBIA as a potential contributor to the pathogenesis of Alzheimer's disease and age-related macular degeneration.","authors":"Shizhen Lei, Yani Liu","doi":"10.1177/13872877251326267","DOIUrl":"10.1177/13872877251326267","url":null,"abstract":"BackgroundAlzheimer's disease (AD) and age-related macular degeneration (AMD) place considerable health burden on affected individuals and significant economic burden on society.ObjectiveThis study aims to explore the shared cellular and molecular mechanisms underlying the pathogenesis of AD and AMD.MethodsThe investigation in this study is conducted via single-cell and bulk tissue transcriptomic analysis. Transcriptomic datasets of AD and AMD were obtained from the GEO database. The shared differentially expressed genes (DEGs) in control and AD- and AMD-affected samples were identified. Functional enrichment analysis for DEGs was subsequently performed. Then, the protein-protein interaction (PPI) network of these DEGs was established via the STRING database and hub genes of this network were identified by Cytoscape software. Single-cell transcriptomic analysis was performed using Seurat R package to explore their expression in different cell types.ResultsDifferential analysis identified 127 shared DEGs of the two diseases, including 71 upregulated and 56 downregulated genes. Upregulated DEGs were enriched in inflammation, gliogenesis, cell apoptosis, and response to bacterial and viral infection and downregulated DEGs were enriched in mitochondrial function and energy production. PPI network and Cytoscape determined 10 hub genes, of which the NFKBIA gene was associated with the severity of both AD and AMD. Moreover, single-cell transcriptomic analysis showed that NFKBIA was highly expressed in microglia from disease-affected tissues.ConclusionsThe findings indicated that microglia with high NFKBIA expression were important contributors to the progression of both AD and AMD. Microglia-derived NFKBIA might serve as a potential therapeutic target for AD and AMD.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"134-146"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Leptin, adiponectin, body mass index, and incident cognitive impairment. 瘦素，脂联素，体重指数，和偶发认知障碍。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-05-01 Epub Date: 2025-04-17 DOI: 10.1177/13872877251326060

Evan L Thacker, Reena Karki, Rachel Gabor, Natalie J Blades, Russell P Sawyer, Cyrille N Kouambo Beckodro, Quinn Preece, Samuel Prince, McKay M Smith, Sarah R Gillett, Suzanne E Judd, Richard E Kennedy, Jorge R Kizer, Deborah A Levine, William M McClellan, Manjula Kurella Tamura, Frederick W Unverzagt, Virginia G Wadley, Mary Cushman

{"title":"Leptin, adiponectin, body mass index, and incident cognitive impairment.","authors":"Evan L Thacker, Reena Karki, Rachel Gabor, Natalie J Blades, Russell P Sawyer, Cyrille N Kouambo Beckodro, Quinn Preece, Samuel Prince, McKay M Smith, Sarah R Gillett, Suzanne E Judd, Richard E Kennedy, Jorge R Kizer, Deborah A Levine, William M McClellan, Manjula Kurella Tamura, Frederick W Unverzagt, Virginia G Wadley, Mary Cushman","doi":"10.1177/13872877251326060","DOIUrl":"https://doi.org/10.1177/13872877251326060","url":null,"abstract":"BackgroundDisordered metabolism affects risk for cognitive decline, Alzheimer's disease, and other dementias, likely through pathways involving adipokines.ObjectiveAnalyze incident cognitive impairment in relation to leptin, adiponectin, body mass index, and other risk factors.MethodsNested case-control study within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort of 30,239 adults in the US. Cases with incident cognitive impairment (n = 489) scored >1.57 SD below demographically adjusted means on ≥2 of 3 cognitive tests: word list learning, word list delayed recall, and category fluency. Cognitively intact controls (n = 583) were randomly selected within demographic strata. Leptin and adiponectin were assayed in thawed blood that had been stored at baseline.ResultsIn participants with normal weight, lower leptin was associated with higher odds of cognitive impairment. Relative to leptin = 25 ng/mL, adjusted ORs were 1.5 (95% CI: 1.2, 1.9) at leptin = 15 ng/mL, 0.8 (0.8, 0.9) at leptin = 30 ng/mL, and 0.5 (0.4, 0.8) at leptin = 45 ng/mL. In participants with obesity, higher adiponectin was associated with higher odds of cognitive impairment. Relative to adiponectin = 25 ng/mL, adjusted ORs were 0.8 (95% CI: 0.7, 1.0) at adiponectin = 15 ng/mL, 1.1 (1.0, 1.2) at adiponectin = 30 ng/mL, and 1.3 (1.0, 1.7) at adiponectin = 45 ng/mL. Associations of adipokines with cognitive impairment varied across levels of other risk factors.ConclusionsAdipokines, in concert with body mass index, play complex roles in cognitive health, with many avenues open for further investigation.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":"105 1","pages":"90-106"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigation of risk of Alzheimer's disease diagnosis and survival based on variation to life experiences used to operationalize cognitive reserve. 根据用于认知储备操作的生活经历的变化，调查阿尔茨海默氏症的诊断和存活风险。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-05-01 Epub Date: 2025-03-26 DOI: 10.1177/13872877251326818

Kerry A Howard, Lauren M Massimo, Brian Witrick, Lu Zhang, Sarah F Griffin, Lesley A Ross, Lior Rennert

{"title":"Investigation of risk of Alzheimer's disease diagnosis and survival based on variation to life experiences used to operationalize cognitive reserve.","authors":"Kerry A Howard, Lauren M Massimo, Brian Witrick, Lu Zhang, Sarah F Griffin, Lesley A Ross, Lior Rennert","doi":"10.1177/13872877251326818","DOIUrl":"10.1177/13872877251326818","url":null,"abstract":"BackgroundAlzheimer's disease dementia (AD) is a debilitating progressive neurodegenerative disease. Life experiences are hypothesized to build cognitive reserve (CR), a theoretical construct associated with delayed onset of AD symptoms. While CR is a key moderator of cognitive decline, operationalization of CR is varied resulting in inconsistencies within the literature.ObjectiveThis study explored the relationship between life experiences used as proxies of CR and risk of AD diagnosis and death following diagnosis.MethodsWe explored results based on 30 different published CR operationalizations, including two standardized questionnaires and an investigator-developed lifecourse indicator. Using data from the Memory and Aging Project, we applied Cox proportional hazard models to evaluate the impact of operationalization on time to outcomes.ResultsHazard ratios, indicating instantaneous risk of AD or death for a standard deviation increase in the CR proxy utilized as a predictor, ranged from 0.80-1.40 for AD diagnosis and 0.80-1.29 for death following diagnosis. Among nine predictors that showed a significant reduction in risk of AD, there was a decrease of between 12% and 20%. Two predictors were associated with reduced risk of death, with 13%-20% reduction, while three predictors were associated with 18%-22% heightened risk of death following diagnosis.ConclusionsModel results were highly sensitive to CR operationalization. Based on the variation in results, composite measures that incorporate multiple lifecourse variables may still be the most comprehensive and faithful representation of CR. Attention to methodology and refining of measurement are needed to make use of CR and promote healthy aging.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"147-158"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Down syndrome and Alzheimer's disease: Oxidative stress in the neurodegenerative process. 唐氏综合症和阿尔茨海默病：神经退行性过程中的氧化应激。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-05-01 Epub Date: 2025-04-03 DOI: 10.1177/13872877251326291

Augusto Magno Tranquezi Cordeiro, Monique Patricio Singulani, Leda Leme Talib, Orestes Vicente Forlenza

{"title":"Down syndrome and Alzheimer's disease: Oxidative stress in the neurodegenerative process.","authors":"Augusto Magno Tranquezi Cordeiro, Monique Patricio Singulani, Leda Leme Talib, Orestes Vicente Forlenza","doi":"10.1177/13872877251326291","DOIUrl":"10.1177/13872877251326291","url":null,"abstract":"BackgroundIndividuals with Down syndrome (DS) generally show neuropathological features of Alzheimer disease (AD). The trisomy of chromosome 21 causes an imbalance of antioxidant systems, which can be linked to AD pathophysiology.ObjectiveVerify the difference between the activity of antioxidant enzymes and products of the oxidation process in peripheral blood in non-trisomic (NT) and trisomic (DS) adults and elders and respective associations with cognitive impairment.MethodsA total of 120 subjects were included in this study. Sociodemographic and clinical information were collected as per protocol for participants in DS and NT groups. The cognitive state of the DS participants was established according to the Brazilian version of the Cambridge Examination for Mental Disorders of Older People with Down's syndrome and Others with Intellectual Disabilities (CAMDEX-DS). The CAMDEX interview was used for this purpose for participants in the NT group. Plasma samples were collected to evaluate protein carbonyl content, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), malondialdehyde (MDA), and 4-hydroxy-2-nonenal (HNE).ResultsWe found increased levels of SOD and CAT activity in the DS group. When the groups were stratified by cognitive decline, elevated levels of SOD and CAT activity were found both in DS groups with and without decline. The activity of GPx was similar between the groups, as well as MDA and HNE.ConclusionThe results suggest that alterations of the antioxidative processes can be implicated in the onset of neurodegeneration observed in individuals with DS.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"258-267"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lipopolysaccharides from Porphyromonas gingivalis indirectly induce neuronal GSK3β-dependent synaptic defects and cause cognitive decline in a low-amyloid-β-concentration environment in Alzheimer's disease. 来自牙龈卟啉单胞菌的脂多糖间接诱导神经元gsk3 β依赖的突触缺陷，并在低淀粉样蛋白β浓度环境中引起阿尔茨海默病的认知能力下降。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-05-01 Epub Date: 2025-03-20 DOI: 10.1177/13872877251326879

Shuge Gui, Fan Zeng, Zhou Wu, Saori Nonaka, Tomomi Sano, Junjun Ni, Hiroshi Nakanishi, Masafumi Moriyama, Takashi Kanematsu

{"title":"Lipopolysaccharides from Porphyromonas gingivalis indirectly induce neuronal GSK3β-dependent synaptic defects and cause cognitive decline in a low-amyloid-β-concentration environment in Alzheimer's disease.","authors":"Shuge Gui, Fan Zeng, Zhou Wu, Saori Nonaka, Tomomi Sano, Junjun Ni, Hiroshi Nakanishi, Masafumi Moriyama, Takashi Kanematsu","doi":"10.1177/13872877251326879","DOIUrl":"10.1177/13872877251326879","url":null,"abstract":"BackgroundLipopolysaccharides from Porphyromonas gingivalis (P.gLPS) are involved in the pathology of Alzheimer's disease (AD). However, the effect of P.gLPS on synaptic defects remains unclear.ObjectiveIn this study, we tested our hypothesis that P.gLPS induces synaptic defects in a low-amyloid-beta (Aβ)-concentration environment.MethodsMG6 microglia or N2a neurons was treated with P.gLPS (0.1 μg/mL), soluble Aβ42 (0.1 μM) or AL (combined P.gLPS and soluble Aβ42 at 0.1 μM).ResultsIn cultured MG6 microglia, increased the mRNA expression of TNF-α, IL-1β and IL-6 and the TNF-α release in parallel with increased NF-κB activation. In cultured N2a neurons, treatment with Aβ42, P.gLPS, and AL did not affect the mRNA expression of synapsin1 (SYN1) or post-synaptic density protein-95 (PSD-95). However, the treatment with conditioned medium from AL-exposed MG6 microglia (AL-MCM) significantly reduced the mRNA and protein expression of SYN1, PSD-95, and nuclear translocation of repressor element-1 silencing transcription factor (REST) but significantly increased the mRNA expression of TNF receptor type I (at 48 h) and glycogen synthase kinase (GSK)3β (at 24 h). TWS119 pretreatment (5 μM), a GSK3β specific inhibitor, significantly reversed the AL-MCM-induced reduction in the mRNA expression of SYN1 and PSD-95 and nuclear translocation of REST in cultured N2a neurons. In APPNL-F/NL-F mice, the immunofluorescence intensity of SYN1 and PSD-95 in cortical neurons was positively correlated with the index of the memory test but negatively correlated with that of TNF-α-positive microglia.ConclusionsThese observations demonstrate that P.gLPS induces neuronal GSK3β-dependent synaptic defects in a low-Aβ concentration environment via microglial activation.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"302-316"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A systematic review and meta-analysis on the characteristics of transcranial magnetic stimulation treatment protocols for patients with Alzheimer's disease. 关于阿尔茨海默病患者经颅磁刺激治疗方案特点的系统回顾和荟萃分析。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-05-01 Epub Date: 2025-03-20 DOI: 10.1177/13872877251325887

Kenji Fuseya, Yu Mimura, Shinichiro Nakajima, Masaru Mimura, Koji Kasanuki, Yoshihiro Noda

{"title":"A systematic review and meta-analysis on the characteristics of transcranial magnetic stimulation treatment protocols for patients with Alzheimer's disease.","authors":"Kenji Fuseya, Yu Mimura, Shinichiro Nakajima, Masaru Mimura, Koji Kasanuki, Yoshihiro Noda","doi":"10.1177/13872877251325887","DOIUrl":"10.1177/13872877251325887","url":null,"abstract":"BackgroundAlzheimer's disease (AD) is the most common neurodegenerative condition causing dementia. Currently, there has been no established non-pharmacological treatment for cognitive decline in patients with AD. Recent evidence suggests that repetitive transcranial magnetic stimulation (rTMS) may be effective as a non-invasive treatment for improving cognitive function in AD.ObjectiveThis study aimed to examine the characteristics of rTMS treatment protocols for patients with ADMethodsWe conducted a systematic literature search on clinical trials on rTMS for improving cognitive decline in patients with AD, using the PubMed, PsycINFO, and Scopus databases and performed a meta-analysis according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. To clarify which cognitive domains in AD are improved by rTMS, meta-analyses were conducted on both global cognitive function and on each cognitive domain including verbal memory, processing speed, and executive function. In addition, sub-analyses of the treatment details of rTMS parameters including stimulation sites, stimulation frequency, stimulation intensity, and with/without the neuro-navigation technique and meta-regression analyses adjusting for gender, education, and the number of rTMS pulses were performed.ResultsThe results showed significant improvements in global cognitive function, while no significant findings in verbal memory, processing speed and executive function. No significant results were found in subgroup analysis or meta-regression.ConclusionsTo enrich the evidence for cognitive enhancement in AD with rTMS, the randomized controlled trials using a unified rTMS protocol with a larger sample size are warranted.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"28-43"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0