Journal of Alzheimer's Disease最新文献_第7页

Gut microbiota-mediated targeting of EHMT2 in individuals of European ancestry: A novel therapeutic approach for Alzheimer's disease. 欧洲血统个体中肠道微生物介导的EHMT2靶向：阿尔茨海默病的一种新治疗方法。

IF 3.1 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-09-22 DOI: 10.1177/13872877251372945

Yan Yan, Yuyan Pan, Simin Lu, Jia Kou, Xiangnan Chen, Weian Zeng, Dexing Luo, Liuji Qiu, Hongying Zhang, Dongtai Chen

{"title":"Gut microbiota-mediated targeting of EHMT2 in individuals of European ancestry: A novel therapeutic approach for Alzheimer's disease.","authors":"Yan Yan, Yuyan Pan, Simin Lu, Jia Kou, Xiangnan Chen, Weian Zeng, Dexing Luo, Liuji Qiu, Hongying Zhang, Dongtai Chen","doi":"10.1177/13872877251372945","DOIUrl":"https://doi.org/10.1177/13872877251372945","url":null,"abstract":"BackgroundEuchromatic histone-lysine N-methyltransferase 2 (EHMT2), a neuroinflammatory histone methyltransferase, has been proposed as a therapeutic target for Alzheimer's disease (AD), potentially via modulation of gut microbiota. However, causality remains unclear due to confounding in observational studies and lack of human genetic evidence.ObjectiveTo address this, we conducted a Mendelian randomization (MR) analysis using genome-wide association data exclusively from individuals of European ancestry.MethodsWe obtained genome-wide association study (GWAS) summary statistics for EHMT2 expression, AD (n = 39,106), 211 gut microbiota taxa, and colorectal cancer (CRC; n = 6847) from the IEU OpenGWAS and FinnGen databases. MR was used to evaluate the causal effects, with CRC as a positive control. Five regression models were utilized to evaluate the causal effects, and two-step MR assessed the mediating role of gut microbiota. Sensitivity analyses tested result robustness.ResultsInverse-variance weighted (IVW) analyses showed that EHMT2 inhibition was associated with reduced risks of CRC [odds ratio (OR) = 0.7850, 95% CI: 0.6782-0.9086, p = 0.0012], and AD (OR = 0.8585, 95% CI: 0.8056-0.9148, p < 0.0001). EHMT2 inhibition also influenced the abundance of 67 gut microbiota taxa. Among them, 17 taxa were linked to AD risk, with four showing shared causal associations. Notably, three of them (family Lactobacillaceae id.1836, genus Dialister id.2183, and unknown genus id.959) had positive mediating effects.ConclusionsEHMT2 inhibition may play protective roles in AD via modulating specific gut microbiota, particularly three key taxa. These findings highlight a potential microbiota-mediated epigenetic mechanism in AD pathogenesis, warranting further mechanistic and translational studies.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251372945"},"PeriodicalIF":3.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124919","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

Medication prescriptions among patients with mild cognitive impairment and Alzheimer's disease: A large nationwide electronic health record cohort study. 轻度认知障碍和阿尔茨海默病患者的药物处方：一项大型全国电子健康记录队列研究

IF 3.1 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-09-22 DOI: 10.1177/13872877251376032

Isabella Boroje, Olga Sánchez-Soliño, Emma Xiaomeng Yue, Lisa Vinikoor-Imler

{"title":"Medication prescriptions among patients with mild cognitive impairment and Alzheimer's disease: A large nationwide electronic health record cohort study.","authors":"Isabella Boroje, Olga Sánchez-Soliño, Emma Xiaomeng Yue, Lisa Vinikoor-Imler","doi":"10.1177/13872877251376032","DOIUrl":"https://doi.org/10.1177/13872877251376032","url":null,"abstract":"BackgroundCholinesterase inhibitors (ChE-Is), including donepezil, rivastigmine, and galantamine, and the N-methyl-D-aspartate receptor antagonist, memantine, are prescribed to decrease cognitive impairment symptoms.ObjectiveThis study examined prescriptions among patients with mild cognitive impairment (MCI) and/or Alzheimer's disease (AD) in the US by age, sex, and race/ethnicity.MethodsThis retrospective cohort study used Optum's de-identified Market Clarity Data containing electronic health records and insurance claims from January 2017 to September 2021. International Classification of Diseases, Ninth and Tenth Revisions diagnosis codes identified MCI and AD cases. Drug prescriptions were identified before, on, or after the date of first diagnosis. Cases were required to have ≥12 months of database enrolment prior to first diagnosis. Descriptive statistics were stratified by demographic groups.ResultsDuring the study period, 197,346 MCI and 144,321 AD cases were identified. Prescriptions were highest in patients with MCI aged 75-84 years before and after diagnosis for ChE-Is (8.1%, 20.4%) and memantine (2.6%, 7.8%) and among patients with AD aged 65-74 years for ChE-Is (25.0%, 38.7%) and memantine (11.2%, 22.1%). After AD diagnosis, the ChE-I prescriptions ranged from 31.3% of African American patients to 34.1% of Asian patients, and from 13.7% of African American patients to 18.5% of Hispanic patients for memantine.ConclusionsChE-I and memantine prescriptions generally increased to a certain age and were similar across sex and race/ethnicity groups. This information helps understand current prescriptions and how best to optimize in all demographic groups.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251376032"},"PeriodicalIF":3.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124946","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

Biomarkers for Alzheimer's disease are upregulated in patients with diabetic retinopathy. 糖尿病视网膜病变患者阿尔茨海默病的生物标志物上调。

IF 3.1 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-09-22 DOI: 10.1177/13872877251378759

Manju L Subramanian, Konstantina Sampani, Steven Ness, Fatima Tuz-Zahra, Sreevardhan Alluri, Xuejing Chen, Nicole H Siegel, Nurgul Aytan, Weiming Xia, Yorghos Tripodis, Michael L Alosco, Thor D Stein

{"title":"Biomarkers for Alzheimer's disease are upregulated in patients with diabetic retinopathy.","authors":"Manju L Subramanian, Konstantina Sampani, Steven Ness, Fatima Tuz-Zahra, Sreevardhan Alluri, Xuejing Chen, Nicole H Siegel, Nurgul Aytan, Weiming Xia, Yorghos Tripodis, Michael L Alosco, Thor D Stein","doi":"10.1177/13872877251378759","DOIUrl":"https://doi.org/10.1177/13872877251378759","url":null,"abstract":"BackgroundDiabetes has been linked to increased prevalence of dementia, but the link between diabetic retinopathy (DR) and Alzheimer's disease (AD) remains unclear.ObjectiveThis study aimed to evaluate potential associations between DR and AD-related protein biomarkers in plasma and ocular fluid.MethodsA prospective, cross-sectional study collected human blood, vitreous, aqueous, and tear samples and measured amyloid-β (Aβ40, Aβ42), total-tau (t-tau), phosphorylated-tau (ptau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) by digital immunoassays.ResultsThe study included 79 eyes (79 patients) [41 females (59.4%); mean (SD) age 57.1 (12.2) years] of which DR was present in 44 (55.7%). All six biomarkers were significantly higher in plasma in participants with DR compared to those without DR [Aβ40 p = 0.002, Aβ42 p = 0.002, t-tau = 0.013, ptau181 p = 0.005, GFAP p = 0.010, and NfL p < 0.001]. Within vitreous, DR participants had significantly elevated t-tau (p = 0.002), ptau181 (p = 0.049), and NfL (p = 0.006); and within aqueous, higher NfL (p = < 0.001). Neuropsychological testing scores were lower in participants with DR than those without but did not reach statistical significance (Montreal-Cognitive-Assessment: p = 0.070; Mini-Mental-State-Exam: p = 0.057).ConclusionsThis study showed significant increases of AD associated protein biomarkers in plasma, vitreous, and aqueous in patients with DR. These results support a potential biological link between DR and AD pathology and suggest that DR, which tends to occur in younger individuals, may be a predictive factor for AD.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251378759"},"PeriodicalIF":3.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113394","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

Machine learning model for predicting the conversion to dementia using the Cube Copying Test. 使用立方体复制测试预测痴呆症转化的机器学习模型。

IF 3.1 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-09-22 DOI: 10.1177/13872877251376939

Mio Shinozaki, Hiroyuki Hishida, Yasuyuki Gondo, Michio Yamamoto, Takashi Suzuki, Rina Miura, Takashi Sakurai, Akinori Takeda, Yutaka Arahata

{"title":"Machine learning model for predicting the conversion to dementia using the Cube Copying Test.","authors":"Mio Shinozaki, Hiroyuki Hishida, Yasuyuki Gondo, Michio Yamamoto, Takashi Suzuki, Rina Miura, Takashi Sakurai, Akinori Takeda, Yutaka Arahata","doi":"10.1177/13872877251376939","DOIUrl":"https://doi.org/10.1177/13872877251376939","url":null,"abstract":"BackgroundEarly detection of dementia requires highly accurate and efficient screening tests that minimize patient burden.ObjectiveTo develop a machine learning model predicting dementia conversion within 3-5 years using Cube Copying Test (CCT) drawings at baseline.MethodsThis retrospective study analyzed CCT drawing data from 767 patients at the Center for Comprehensive Care and Research on Memory Disorders (2011-2020). Of the 2303 patients who met the inclusion criteria, 534 were excluded due to mild cognitive impairment (MCI) persistence, pending diagnoses, or new neurovascular diseases, while 1002 were lost to follow-up. Eligibility criteria included a baseline Mini-Mental State Examination (MMSE) score ≥24, absence of dementia diagnosis or anti-dementia medication intake, and completion of a 3-5-year follow-up without meeting exclusion criteria.ResultsOf 767 patients, 457 converted to dementia (318 with Alzheimer's disease, 116 with dementia with Lewy bodies, and 23 with frontotemporal dementia) within 3-5 years, while 310 did not. The model achieved an area under the curve of 0.85 for predicting dementia conversion. Shapley Additive exPlanations analysis identified PatchCore-derived features as the strongest predictors, distinguishing drawing patterns of converters and non-converters.ConclusionsIn patients who convert to Alzheimer's disease, dementia with Lewy bodies, or frontotemporal dementia, the very early stages of constructional apraxia-like symptoms already exist at the preclinical stage or MCI stage. Applying deep learning-based anomaly-detection models can detect these early drawing distortions that differ from normal aging and contribute to improving the performance of dementia-conversion prediction.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251376939"},"PeriodicalIF":3.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113371","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

Longitudinal online weekly reports of non-cognitive symptoms and events can differentiate incident mild cognitive impairment from stable cognitively healthy older adults. 非认知症状和事件的纵向在线每周报告可以区分偶发性轻度认知障碍和稳定的认知健康老年人。

IF 3.1 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-09-22 DOI: 10.1177/13872877251376524

Christine McClure, Nora Mattek, Zachary Beattie, Nicole Sharma, Thomas Riley, Joel Steele, Jeffrey Kaye

{"title":"Longitudinal online weekly reports of non-cognitive symptoms and events can differentiate incident mild cognitive impairment from stable cognitively healthy older adults.","authors":"Christine McClure, Nora Mattek, Zachary Beattie, Nicole Sharma, Thomas Riley, Joel Steele, Jeffrey Kaye","doi":"10.1177/13872877251376524","DOIUrl":"https://doi.org/10.1177/13872877251376524","url":null,"abstract":"BackgroundChanges in noncognitive symptoms such as mood, loneliness, pain, and need for assistance may be potential early markers of mild cognitive impairment (MCI) and Alzheimer's disease and related disorders (ADRD) in older adults. These changes can be subtle and fluctuating, and thus easily missed during intermittent clinic visits.ObjectiveTo assess the relationship of changes in self-perceived internal states and needs to the development of cognitive impairment over time.MethodsWeekly online reports of health-related activities and mood in relation to MCI were assessed for up to 2.9 years in older adults participating in the Oregon Life Laboratory, a study using home-based unobtrusive remote sensing of physical, cognitive, behavioral, physiological, and health-related activities.ResultsThe analytic sample included 129 cognitively healthy volunteers followed for a mean of 2.9 ± 1.2 years. Mean age was 83.5 ± 7.8 years, mean education was 15.7 ± 2.7 years, and 76% were female. Twenty-two participants (17%) developed MCI or dementia while 107 remained cognitively healthy. Over time, more of the participants destined to develop MCI reported: (1) loneliness (p = 0.049), (2) low mood (p = 0.08), (3) pain intensity (p = 0.03) and pain interference (p = 0.01), and (4) needing in-home assistance (p = 0.02) than those remaining cognitively healthy. Baseline scores assessing these symptoms were not clinically concerning, predictive of MCI, nor significantly different between groups.ConclusionsLongitudinal home-based online assessment of non-cognitive aspects of function or internal states (loneliness, mood, pain, needing more assistance) can be sensitive early indicators of changes in brain function leading to MCI and ADRD.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251376524"},"PeriodicalIF":3.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124957","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

High brain network dynamics mediate audiovisual integration deficits and cognitive impairment in Alzheimer's disease. 高脑网络动态介导阿尔茨海默病的视听整合缺陷和认知障碍。

IF 3.1 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-09-22 DOI: 10.1177/13872877251376717

Jieying Li, Yang Yi, Xin Gao, Yanna Ren, Lin Gan, Ting Zou, Xiaohong Qin, Arui Tan, Xinxuan Yang, Fugui Jiang, Xuemei Liu, Haiyan Gao, Yiting Wang, Etienne Aumont, Jun Xiao, Bo Zhou, Wei Liao, Huafu Chen, Wei Zhang, Maxime Montembeault, Pedro Rosa-Neto, Rong Li

{"title":"High brain network dynamics mediate audiovisual integration deficits and cognitive impairment in Alzheimer's disease.","authors":"Jieying Li, Yang Yi, Xin Gao, Yanna Ren, Lin Gan, Ting Zou, Xiaohong Qin, Arui Tan, Xinxuan Yang, Fugui Jiang, Xuemei Liu, Haiyan Gao, Yiting Wang, Etienne Aumont, Jun Xiao, Bo Zhou, Wei Liao, Huafu Chen, Wei Zhang, Maxime Montembeault, Pedro Rosa-Neto, Rong Li","doi":"10.1177/13872877251376717","DOIUrl":"https://doi.org/10.1177/13872877251376717","url":null,"abstract":"BackgroundAudiovisual integration deficits are frequent in patients with Alzheimer's disease (AD). In addition, patients with AD have altered functional brain networks, such as those supporting auditory and visual processing. However, the mechanisms driving this association remain unclear.ObjectiveTo investigate whether dynamic functional network disruptions underlie audiovisual integration and cognitive deficits in AD.MethodsSeventy-nine participants (41 AD, 38 controls) completed audiovisual stimuli tasks. A multilayer modularity algorithm was utilized to assess the resting-state fMRI-based brain dynamics of the primary sensory and higher-order functional networks. Mediation analysis was conducted to test our hypothesis.ResultsAD patients showed delayed response time and reduced peak benefit of audiovisual integration. Dynamic switching rates of primary sensory and higher-order networks were significantly increased in AD, particularly in the dynamic integration between the default mode network (DMN) and visual network (VN). The peak benefit of audiovisual integration negatively correlated with DMN-VN dynamic integration and positively with Mini-Mental State Examination, Montreal Cognitive Assessment, and Auditory Verbal Learning Test delayed scores. Notably, excessive integration between the DMN and VN mediated the relationship between audiovisual integration deficits and cognitive impairment in patients with AD.ConclusionsThese findings suggest that audiovisual integration impairment may disturb the dynamic integration between the DMN and VN, contributing to cognitive impairment in AD. The neural mechanisms underlying audiovisual integration deficit and cognitive decline might help with early diagnosis and intervention for AD.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251376717"},"PeriodicalIF":3.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113417","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

HIF-1α-induced microglia-mediated neuroinflammation is involved in Alzheimer's disease: Evidence from single-cell transcriptomic analysis. hif -1α-诱导的小胶质细胞介导的神经炎症参与阿尔茨海默病：来自单细胞转录组学分析的证据

IF 3.1 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-09-19 DOI: 10.1177/13872877251378007

Manyu Dong, Yilun Qian, Yao Geng, Ruiyu Wang, Yu Wang, Jili Cai, Xihui Wang, Ying Huang, Yan Liu, Wentao Liu, Qi Wu, Ying Shen

{"title":"HIF-1α-induced microglia-mediated neuroinflammation is involved in Alzheimer's disease: Evidence from single-cell transcriptomic analysis.","authors":"Manyu Dong, Yilun Qian, Yao Geng, Ruiyu Wang, Yu Wang, Jili Cai, Xihui Wang, Ying Huang, Yan Liu, Wentao Liu, Qi Wu, Ying Shen","doi":"10.1177/13872877251378007","DOIUrl":"https://doi.org/10.1177/13872877251378007","url":null,"abstract":"BackgroundMicroglia are central mediators of neuroinflammation in Alzheimer's disease (AD), contributing significantly to disease pathogenesis. Understanding microglial heterogeneity and their regulatory mechanisms is critical for identifying potential therapeutic targets.ObjectiveThis study aimed to investigate the diversity of microglial subpopulations in AD and uncover key transcriptional regulators driving their pathogenic activity.MethodsWe integrated bulk RNA sequencing data from AD patients and 5×FAD mouse models with single-cell RNA sequencing (scRNA-seq) to profile microglial heterogeneity. Differential gene expression, pathway enrichment, pseudotime trajectory, and SCENIC analyses were used to identify functionally distinct subsets and regulatory networks. Experimental validation was conducted through in vivo assays in 5×FAD mice and in vitro inhibition studies targeting HIF-1α.ResultsA unique microglial subpopulation, termed microglia_2, was identified with an inflammatory-angiogenic transcriptional signature that was enriched during AD progression. This subset showed significant activation of inflammatory pathways. Pseudotime and SCENIC analyses revealed HIF-1α as a master regulator of microglia_2. In 5×FAD mice, cognitive decline was accompanied by increased expression of HIF-1α and Apoe, as well as microglial activation in the prefrontal cortex. In vitro inhibition of HIF-1α significantly reduced microglial inflammation.ConclusionsOur study demonstrates that a specific microglial subpopulation characterized by elevated HIF-1α expression may contribute to AD-associated neuroinflammation. By integrating transcriptomic analyses and experimental validation, we provide cell type-specific insights into disease mechanisms, offering potential insights for future mechanistic studies and therapeutic exploration.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251378007"},"PeriodicalIF":3.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091539","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

Identification of novel biomarkers for cognitive function via an integrative analysis. 通过综合分析鉴定认知功能的新生物标志物。

IF 3.1 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-09-19 DOI: 10.1177/13872877251379853

Ruxue Mao, Shuoyan Zhao, Jiajie Chen, Luyao Wang, Kai Zheng, Bin Li

{"title":"Identification of novel biomarkers for cognitive function via an integrative analysis.","authors":"Ruxue Mao, Shuoyan Zhao, Jiajie Chen, Luyao Wang, Kai Zheng, Bin Li","doi":"10.1177/13872877251379853","DOIUrl":"https://doi.org/10.1177/13872877251379853","url":null,"abstract":"Cognitive dysfunction associated with various diseases and its biomarkers have been extensively studied. However, research focusing on biomarkers related to cognitive function remains limited. This study aims to identify potential biomarkers associated with cognitive function and validate them through in vitro and in vivo experiments to address the current research gaps. We employed GWAS, PWAS, and TWAS analyses, combined with Mendelian randomization and colocalization analysis, to identify potential cognitive function-related biomarkers from European cohorts. An Alzheimer's disease (AD) cell model was established in SH-SY5Y and BV2 cells using Aβ25-35 oligomers, and an APP/PS1 (AD mouse model) was purchased. The mRNA and protein expression levels of potential biomarkers were assessed in AD cells and mouse models using RT-qPCR and western blotting. Immunofluorescence was used to evaluate the fluorescence expression of these biomarkers in the AD cells, while immunohistochemistry was employed to assess staining intensity in the dorsolateral prefrontal cortex of AD model mice. Three potential biomarkers associated with cognitive function were identified: GPX1, CSE1L, and SULT1A1. KEGG enrichment analysis indicated that GPX1, CSE1L, and SULT1A1 are involved in various metabolic pathways, including those related to amyotrophic lateral sclerosis and Huntington's disease signaling. RT-qPCR and western blotting revealed low expression of GPX1 and CSE1L, and high expression of SULT1A1 in both AD cells and mouse models. These findings were further confirmed by immunofluorescence and immunohistochemistry, which demonstrated similar expression patterns in the AD cell and mouse models. GPX1, CSE1L, and SULT1A1 serve as biomarkers of cognitive function.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251379853"},"PeriodicalIF":3.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091544","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

The effect of deprivation of whisker stimulation on cognition and synaptic plasticity in male and female Alzheimer's disease mice. 剥夺须刺激对阿尔茨海默病小鼠认知和突触可塑性的影响。

IF 3.1 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-09-19 DOI: 10.1177/13872877251379079

Xiaomei Su, Haichao Chen, Jiaxin Cao, Yishu Zhang, Yiting Kang, Lei Wang, Jie Yin, Yuhong Jing

{"title":"The effect of deprivation of whisker stimulation on cognition and synaptic plasticity in male and female Alzheimer's disease mice.","authors":"Xiaomei Su, Haichao Chen, Jiaxin Cao, Yishu Zhang, Yiting Kang, Lei Wang, Jie Yin, Yuhong Jing","doi":"10.1177/13872877251379079","DOIUrl":"https://doi.org/10.1177/13872877251379079","url":null,"abstract":"BackgroundAmyloid-β (Aβ) and Aβ plaques can disrupt synaptic plasticity, leading to abnormalities in sensory function and cognition in Alzheimer's disease (AD). The whisker sensorimotor system is crucial for tactile perception, providing rodents with spatial and textural features information about their surroundings. Sensory inputs from whiskers have a clear topological localization in the barrel cortex.ObjectivePrevious studies have suggested that sensory stimulation can effectively ameliorate the pathology of AD mice and improve cognitive performance. However, it remains unknown whether tactile stimulation via whiskers can activate cortical sensory areas, protect synaptic structure and function.MethodsHere, we established a whisker deprivation (WD) model in the 5×FAD mouse.ResultsWe found that WD aggravated the deposition of Aβ1-42, 6E10 and fibrotic Aβ in the cortex, hippocampus and thalamus. Simultaneously, changes in dendritic morphology were consistent with the decreased pCreb levels in the hippocampal dentate gyrus region. WD also reduced axonal projections from layer L4/L5a to L2/3 in the barrel cortex, as well as projections from the entorhinal cortex to the DG, which may disrupt the integration of information in cortical functional columns and weaken the efficiency of information transmission. Additionally, we observed sex differences in effects of WD on AD pathology in 5×FAD mice, with female mice being more sensitive to WD treatment. Ultimately, WD impaired working memory, spatial memory and social behavior in 5×FAD mice.ConclusionsOur study suggested that WD exacerbated the progression of AD pathology in 5×FAD mice, which implicated with Aβ aggravation and synaptic dysfunction.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251379079"},"PeriodicalIF":3.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091749","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

Machine learning-based risk scores are associated with conversion to dementia in Veterans. 基于机器学习的风险评分与退伍军人转变为痴呆症有关。

IF 3.1 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-09-19 DOI: 10.1177/13872877251378773

Karl Brown, Andrew Shutes-David, Katie Wilson, Yijun Shao, Mark Logue, Qing T Zeng, Debby W Tsuang

{"title":"Machine learning-based risk scores are associated with conversion to dementia in Veterans.","authors":"Karl Brown, Andrew Shutes-David, Katie Wilson, Yijun Shao, Mark Logue, Qing T Zeng, Debby W Tsuang","doi":"10.1177/13872877251378773","DOIUrl":"https://doi.org/10.1177/13872877251378773","url":null,"abstract":"BackgroundWe previously developed ancestry-specific risk scores for undiagnosed Alzheimer's disease and related dementias (ADRD) in Black and White American (BA and WA) Veterans by applying natural language processing and machine learning (ML) to Veterans Health Administration electronic health records. Using blinded manual chart reviews, we identified an association between ADRD risk scores and probable ADRD diagnosis at the time the scores were generated. However, it was unclear whether these scores were associated with future ADRD diagnoses and mortality.ObjectiveTo evaluate whether ADRD risk scores are associated with subsequent ADRD incidence and all-cause mortality among BA and WA Veterans without a prior ADRD diagnosis.MethodsWe conducted survival analyses to assess the association between baseline ADRD risk scores and time to either ADRD diagnosis or death. Cause-specific Cox proportional hazards models, treating death as a competing risk, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Analyses were stratified by race and conducted separately for BA and WA Veterans.ResultsHigher ADRD risk scores were significantly associated with increased risk of developing an ADRD diagnosis (HR = 1.98, 95% CI: 1.72-2.27 for BAs; HR = 2.13, 95% CI: 1.79-2.54 for WAs) and mortality (HR = 1.52, 95% CI: 1.40-1.65 for BAs; HR = 1.55, 95% CI: 1.42-1.69 for WAs).ConclusionsIn addition to identifying undiagnosed cases, ML-derived ADRD risk scores are associated with increased risks of developing future ADRD and mortality, which supports their potential utility for both early detection and prognosis.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251378773"},"PeriodicalIF":3.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091516","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}

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