Journal of Alzheimer's Disease最新文献_第9页

A mass-producible macaque model displays a durable Alzheimer-like cognitive deficit and hallmark amyloid-β/tau/neurofilament light chain pathologies. 大规模生产的猕猴模型显示出持久的阿尔茨海默样认知缺陷和标志性的淀粉样β/tau/神经丝轻链病理。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-04-23 DOI: 10.1177/13872877251334316

Feng He, Wen-Jiao Shi, Wen Liu, Jing-Xin Fan, Zhi-Gang He, Ya-Qi Zhang, Jing Xiao, Wei-Wei Ruan, Yong-Kang Gai, Hong-Li Zhang, Bin-Bin Yang, Yao Qin, Hao Wang, Jia Li, Jun-Li Wang, Sha Liu, Li-Ping Shi, Zhong-Xu Chen, Wei-Jie Jiang, Ni An, Peng-Jing Xue, Zi-Hao Wang, Rui-Jie Yang, Peng-Yu Tian, Zhu Chen, Ling Xiao, Zheng-Sheng Yang, Kang-Bo Feng, Wei-Ye Tan, Zhan-Meng Sun, Wei Xu, Huaqing Shu, Jian-Zhi Wang

{"title":"A mass-producible macaque model displays a durable Alzheimer-like cognitive deficit and hallmark amyloid-β/tau/neurofilament light chain pathologies.","authors":"Feng He, Wen-Jiao Shi, Wen Liu, Jing-Xin Fan, Zhi-Gang He, Ya-Qi Zhang, Jing Xiao, Wei-Wei Ruan, Yong-Kang Gai, Hong-Li Zhang, Bin-Bin Yang, Yao Qin, Hao Wang, Jia Li, Jun-Li Wang, Sha Liu, Li-Ping Shi, Zhong-Xu Chen, Wei-Jie Jiang, Ni An, Peng-Jing Xue, Zi-Hao Wang, Rui-Jie Yang, Peng-Yu Tian, Zhu Chen, Ling Xiao, Zheng-Sheng Yang, Kang-Bo Feng, Wei-Ye Tan, Zhan-Meng Sun, Wei Xu, Huaqing Shu, Jian-Zhi Wang","doi":"10.1177/13872877251334316","DOIUrl":"https://doi.org/10.1177/13872877251334316","url":null,"abstract":"BackgroundAlzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by cognitive deficit and pathological accumulation of amyloid-β (Aβ) and tau proteins. The rodent models have contributed greatly to unravel AD pathogenesis, but these AD models have been shown a modest clinical translational effectiveness.ObjectiveTherefore, developing mass-producible primate AD models is promising for more effective drug development.MethodsHere, we constructed the AD monkey models by simultaneously infusing AAV-Tau and Aβ into different brain regions.ResultsThe induced monkeys showed a durable cognitive impairment lasting for at least 10 months after the modeling. Simultaneously, the increased levels of total tau and hyperphosphorylated tau (pTau) at several AD-associated sites, and neurofilament light chains (NfL) with altered Aβ level were detected at different time points in cerebrospinal fluid and/or plasma by using MSD kits. The increased brain accumulation of Aβ and tau proteins was also detected by positron emission tomography/magnetic resonance imaging and immunohistochemical staining. The model monkeys also had significant glial activation; an indicator of inflammation commonly seen in the brains of AD patients.ConclusionsTogether, this study provides mass-producible monkey models showing durable AD-like hallmark pathologies (Aβ, tau, NfL, i.e., ATN) and cognitive deficits. As monkeys are genetically and metabolically the closest to humans, these models will offer more effective drug discovery and development for AD.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251334316"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025381","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 association between long-term trajectories of insulin resistance and brain structural integrity in middle-aged and older adults. 中老年人胰岛素抵抗的长期轨迹与大脑结构完整性之间的关系。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-04-23 DOI: 10.1177/13872877251336333

Mei-Jun Shu, Fei Han, Fei-Fei Zhai, Ding-Ding Zhang, Li-Xin Zhou, Jun Ni, Ming Yao, Li-Ying Cui, Bin Peng, Zheng-Yu Jin, Shu-Yang Zhang, Yi-Cheng Zhu

{"title":"The association between long-term trajectories of insulin resistance and brain structural integrity in middle-aged and older adults.","authors":"Mei-Jun Shu, Fei Han, Fei-Fei Zhai, Ding-Ding Zhang, Li-Xin Zhou, Jun Ni, Ming Yao, Li-Ying Cui, Bin Peng, Zheng-Yu Jin, Shu-Yang Zhang, Yi-Cheng Zhu","doi":"10.1177/13872877251336333","DOIUrl":"https://doi.org/10.1177/13872877251336333","url":null,"abstract":"BackgroundThe triglyceride-glucose (TyG) index is considered a robust surrogate for insulin resistance (IR). The relationship between the trajectory patterns of the TyG index and subsequent brain structure changes is still unclear.ObjectiveThis study investigates the relationship between 10-year trajectories of TyG-related indices and brain structural integrity in a 10-year follow-up.MethodsThis prospective study included 898 participants (mean age 55.6 years, 34.4% males) from the community-based Shunyi Study. IR was assessed using the TyG index, TyG-body mass index (BMI) index, TyG-waist circumference index, and TyG-waist-to-height ratio (WHtR) index. The group-based trajectory model was employed to identify the 10-year trajectories. Structural brain measurements included structural changes of the whiter matter (white matter hyperintensities (WMHs), fractional anisotropy, and mean diffusivity) and gray matter (brain parenchymal fraction (BPF), cortical thickness, and hippocampal volume). General linear models were utilized to examine the association between the trajectory patterns of TyG-related indices and brain structure.ResultsThree distinct trajectories of TyG-related indices were identified from 2013 to 2023. The high-level trajectory groups of TyG-related indices exhibited a greater volume of WMHs and were more susceptible to disruptions in white matter microstructural integrity. This association was most significant for the TyG-BMI and TyG-WHtR trajectory groups. No significant correlations were found for BPF and cortical thickness among the different TyG-related indices trajectories.ConclusionsThe findings suggest that long-term IR primarily damages brain white matter rather than causing structural changes in gray matter.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251336333"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010723","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

Methods for measuring interpersonal behavioral and neural synchrony during group music therapy for individuals with dementia and their caregivers: A case series study. 测量痴呆症患者及其照顾者群体音乐治疗期间人际行为和神经同步性的方法：一个案例系列研究。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-04-23 DOI: 10.1177/13872877251334406

Joanna Culligan, Noor Tasnim, Patricia Winter, Tanner Upthegrove, Daniel Fine English, Julia C Basso

{"title":"Methods for measuring interpersonal behavioral and neural synchrony during group music therapy for individuals with dementia and their caregivers: A case series study.","authors":"Joanna Culligan, Noor Tasnim, Patricia Winter, Tanner Upthegrove, Daniel Fine English, Julia C Basso","doi":"10.1177/13872877251334406","DOIUrl":"https://doi.org/10.1177/13872877251334406","url":null,"abstract":"Background: Alzheimer's disease and related dementias (ADRD) are neurodegenerative disorders that afflict 1 in 9 older adults. As pharmacological interventions for ADRD are often ineffective and cause rampant side effects, interest has increased in finding adjunctive, non-pharmacological approaches. Music therapy may be especially beneficial for individuals with ADRD and their caregivers as music is a form of non-verbal communication. Objective: In this case series, we describe a 12-week group music therapy program for individuals with ADRD and their caregivers. Methods: Brain activity was recorded with hyperscanning electroencephalography (EEG) during each music therapy session from the individual with ADRD (n = 3), caregiver (n = 3), and music therapist (n = 1). Video recordings allowed for assessment of movement behavior and affective state responses. Results: This 12-week case series of group music therapy for individuals and their caregivers had a 66% retention and 95.8% adherence rate. We had success collecting behavioral and neural data using 360-degree video capture in combination with EEG. Video recordings allowed us to analyze affective state and nonverbal communication metrics. After pre-processing, neural recordings were clean and able to be analyzed for various neural metrics of interest. Conclusions: A human-centered design approach can be helpful for implementing longitudinal, non-pharmacological interventions in this vulnerable population. A team-science approach with a collective of creative arts therapists, neuroscientists, dementia care experts, creative technologists, and gerontology experts contributed to the conduction of this work. Future studies should examine the effects of music therapy on behavioral and neural outcomes, especially as it relates to interpersonal behavioral and neural synchrony.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251334406"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014262","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

Neuropsychological phenotypic characteristics in a cohort of community-based older adults: Data from the Framingham Heart Study. 社区老年人队列的神经心理表型特征：来自弗雷明汉心脏研究的数据。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-04-23 DOI: 10.1177/13872877251334608

Ileana De Anda-Duran, Phillip H Hwang, Deborah Ag Drabick, Stacy L Andersen, Rhoda Au, David J Libon

{"title":"Neuropsychological phenotypic characteristics in a cohort of community-based older adults: Data from the Framingham Heart Study.","authors":"Ileana De Anda-Duran, Phillip H Hwang, Deborah Ag Drabick, Stacy L Andersen, Rhoda Au, David J Libon","doi":"10.1177/13872877251334608","DOIUrl":"https://doi.org/10.1177/13872877251334608","url":null,"abstract":"BackgroundNeuropsychological (NP) assessment is crucial for diagnosing prodromal and Alzheimer's disease and related dementia (ADRD) syndromes. Yet, traditional NP scores often overlook errors and the process by which summary scores are obtained; information that can provide deeper insights into cognitive impairments and clinical heterogeneity.ObjectiveTo classify community-dwelling adults into neurocognitive phenotypes, identify NP test errors and processes that differentiate between groups, and explore their association with brain imaging measures.MethodsFramingham Heart Study (FHS) data were analyzed, focusing on NP summary scores and errors derived from the Boston Process Approach. Latent class analysis identified distinct neurocognitive phenotypes. Regression analyses assessed the relationships with NP errors and brain MRI measures.ResultsA total of 1195 participants (mean age 69.6 and 56.3% women) were included. Cognitively normal (CN), moderate-mixed, and dysexecutive impairment groups were identified. The number of Trail Making Test - Part B (TMT-B) pen lifts and TMT-B examiner-corrected errors were associated with the dysexecutive phenotype and differentiated it from the CN group (OR = 1.39, 95% CI = 1.28-1.52, p < 0.001, AUC = 0.85 and OR = 3.40, 95% CI = 2.65-4.38, p < 0.001, AUC = 0.92; respectively). Similarly, Boston Naming Test (BNT) circumlocution errors were associated with the moderate-mixed phenotype and differentiated it from the CN group (OR = 1.87, 95% CI = 1.49-2.35, p < 0.001, AUC = 0.81). These scores were significantly associated with reduced hippocampal volumes.ConclusionsDetailed NP error and process analysis enhances traditional methods, offering a comprehensive approach to identifying and understanding cognitive impairments.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251334608"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986100","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

Adverse events associated with lecanemab: A disproportionality analysis of data from the FDA adverse event reporting system. 与莱卡耐单抗相关的不良事件：FDA不良事件报告系统数据的歧化分析。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-04-23 DOI: 10.1177/13872877251333084

Jiahao Li, Feng Zhang, Ulrich Lm Eisel

{"title":"Adverse events associated with lecanemab: A disproportionality analysis of data from the FDA adverse event reporting system.","authors":"Jiahao Li, Feng Zhang, Ulrich Lm Eisel","doi":"10.1177/13872877251333084","DOIUrl":"https://doi.org/10.1177/13872877251333084","url":null,"abstract":"BackgroundLecanemab, a monoclonal antibody targeting amyloid-β plaques, is FDA-approved for early Alzheimer's disease (AD) treatment. However, safety data from daily clinical practice is limited.ObjectiveThis study aims to assess the adverse events (AEs) linked to lecanemab using the FDA Adverse Event Reporting System (FAERS) to inform better safety management.MethodsA retrospective pharmacovigilance study was conducted using FAERS data from Q1 2023 to Q2 2024. Disproportionality analysis, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), was applied to evaluate AEs where lecanemab was the primary suspect drug.ResultsFrom Q1 2023 to Q2 2024, 917 AEs related to lecanemab were recorded in the FAERS database, with 67.2% of patients aged between 65 and 85 years and 54.5% involving women. Disproportionality analysis identified significant AEs across 22 organ systems, particularly nervous system and psychiatric disorders. Common AEs included headache, amyloid-related imaging abnormalities, and infusion-related reactions, while sleep-related issues like somnolence, abnormal dreams, and poor-quality sleep were notable. Median onset time was 48 days, with serious outcomes in 14.3% of cases, including 70 hospitalizations and 15 deaths.ConclusionsThis pharmacovigilance analysis confirms known AEs of lecanemab and highlights new safety concerns, particularly its impact on sleep. These findings underscore the importance of ongoing monitoring and research to enhance lecanemab's safety profile in AD treatment. However, due to the limitations of FAERS, our analysis is imperfect in terms of important AEs such as therapy-related brain loss and death.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251333084"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004727","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

Glial changes and gene expression in Alzheimer's disease from snRNA-Seq and spatial transcriptomics. 从snRNA-Seq和空间转录组学分析阿尔茨海默病的神经胶质变化和基因表达。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-04-23 DOI: 10.1177/13872877251330320

Songren Wei, Chenyang Li, Wenxuan Li, Fumiao Yuan, Jingjing Kong, Xi Su, Peng Huang, Hongbo Guo, Jiangping Xu, Haitao Sun

{"title":"Glial changes and gene expression in Alzheimer's disease from snRNA-Seq and spatial transcriptomics.","authors":"Songren Wei, Chenyang Li, Wenxuan Li, Fumiao Yuan, Jingjing Kong, Xi Su, Peng Huang, Hongbo Guo, Jiangping Xu, Haitao Sun","doi":"10.1177/13872877251330320","DOIUrl":"https://doi.org/10.1177/13872877251330320","url":null,"abstract":"BackgroundAlzheimer's disease (AD) is characterized by cortical atrophy, glutamatergic neuron loss, and cognitive decline. However, large-scale quantitative assessments of cellular changes during AD pathology remain scarce.ObjectiveThis study aims to integrate single-nuclei sequencing data from the Seattle Alzheimer's Disease Cortical Atlas (SEA-AD) with spatial transcriptomics to quantify cellular changes in the prefrontal cortex and temporal gyrus, regions vulnerable to AD neuropathological changes (ADNC).MethodsWe mapped differentially expressed genes (DEGs) and analyzed their interactions with pathological factors such as APOE expression and Lewy bodies. Cellular proportions were assessed, focusing on neurons, glial cells, and immune cells.ResultsRORB-expressing L4-like neurons, though vulnerable to ADNC, exhibited stable cell numbers throughout disease progression. In contrast, astrocytes displayed increased reactivity, with upregulated cytokine signaling and oxidative stress responses, suggesting a role in neuroinflammation. A reduction in synaptic maintenance pathways indicated a decline in astrocytic support functions. Microglia showed heightened immune surveillance and phagocytic activity, indicating their role in maintaining cortical homeostasis.ConclusionsThe study underscores the critical roles of glial cells, particularly astrocytes and microglia, in AD progression. These findings contribute to a better understanding of cellular dynamics and may inform therapeutic strategies targeting glial cell function in AD.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251330320"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996736","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

EPIC-Potsdam sub-cohort study: The early role of trace elements, oxidative stress, and anthropometrics in Alzheimer's disease and dementia onset. epic -波茨坦亚队列研究：微量元素、氧化应激和人体测量学在阿尔茨海默病和痴呆发病中的早期作用

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-04-23 DOI: 10.1177/13872877251333726

Tom Heinze, Max Tuchtenhagen, Sven Knüppel, Daniela Weber, Gabriele Pohl, Franziska Jannasch, Catarina Schiborn, Matthias B Schulze, Tilman Grune, Tanja Schwerdtle

{"title":"EPIC-Potsdam sub-cohort study: The early role of trace elements, oxidative stress, and anthropometrics in Alzheimer's disease and dementia onset.","authors":"Tom Heinze, Max Tuchtenhagen, Sven Knüppel, Daniela Weber, Gabriele Pohl, Franziska Jannasch, Catarina Schiborn, Matthias B Schulze, Tilman Grune, Tanja Schwerdtle","doi":"10.1177/13872877251333726","DOIUrl":"https://doi.org/10.1177/13872877251333726","url":null,"abstract":"BackgroundSerum trace elements, anthropometric data, and oxidative stress markers are often altered in patients diagnosed with Alzheimer's disease (AD) or other types of dementia (OTD). However, these parameters are rarely examined together before disease onset in a single study population.ObjectiveThis nested case-control study aims to investigate anthropometric data, serum trace elements, exchangeable copper (CuEXC), and oxidative stress markers to identify early associations with the risk of AD or OTD.MethodsFrom the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort (DRKS-ID: DRKS00020593), the High Fat Diet, Microbiota, and Neuroinflammation in the Progression of Alzheimer study was generated. One hundred twenty-eight individuals who developed AD or OTD were identified, approximately 15.7 years after baseline data collection, and matched for age, sex, fasting status, and season of blood sampling with 512 controls. Serum levels of manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), selenium (Se), iodine (I), CuEXC, and plasma malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) were analyzed.ResultsCases and non-cases did not differ in anthropometric data or oxidative stress markers. Female cases exhibited a trend of elevated serum Cu and CuEXC levels compared to female non-cases. A higher Se/Cu ratio suggested an inverse association (OR = 0.72, 95% CI: 0.56-0.92), while an increased Cu/Zn ratio was positively associated (OR = 2.1, 95% CI: 1.1-4.1) with AD or OTD incidence.ConclusionsRatios of serum trace elements, rather than individual levels, show early associations with the risk of AD or OTD while anthropometric and oxidative stress markers did not.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251333726"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005895","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

Plasma TAR DNA-binding protein 43 (TDP-43) levels in a population-based cohort of older adults: The cardiovascular health study. 老年人血浆TAR dna结合蛋白43 （TDP-43）水平：心血管健康研究

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-04-23 DOI: 10.1177/13872877251334820

Alison E Fohner, Colleen M Sitlani, Suman Jayadev, Joshua C Bis, Emily H Trittschuh, Oscar L Lopez, Russel P Tracy, Bruce M Psaty, W T Longstreth, Sudha Seshadri

引用次数: 0

Cerebrospinal fluid inflammatory cytokines as prognostic indicators for cognitive decline across Alzheimer's disease spectrum. 脑脊液炎症细胞因子作为阿尔茨海默病谱系认知能力下降的预后指标。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-04-22 DOI: 10.1177/13872877251335915

Elham Ghanbarian, Babak Khorsand, Kellen K Petersen, Bhargav T Nallapu, S Ahmad Sajjadi, Richard B Lipton, Ali Ezzati

{"title":"Cerebrospinal fluid inflammatory cytokines as prognostic indicators for cognitive decline across Alzheimer's disease spectrum.","authors":"Elham Ghanbarian, Babak Khorsand, Kellen K Petersen, Bhargav T Nallapu, S Ahmad Sajjadi, Richard B Lipton, Ali Ezzati","doi":"10.1177/13872877251335915","DOIUrl":"https://doi.org/10.1177/13872877251335915","url":null,"abstract":"BackgroundNeuroinflammation actively contributes to the pathophysiology of Alzheimer's disease (AD); however, the value of neuroinflammatory biomarkers for disease-staging or predicting disease progression remains unclear.ObjectiveTo investigate diagnostic and prognostic utility of inflammatory biomarkers in combination with conventional AD biomarkers.MethodsData from 258 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) with cerebrospinal fluid (CSF) biomarkers of amyloid-β (Aβ), tau, and inflammation were analyzed. Clinically meaningful cognitive decline (CMCD) was defined as a ≥ 4-point increase on the Alzheimer's Disease Assessment Scale Cognitive Subscore 11. Predictor variables included demographics (D: age, sex, education), APOE4 status (A), inflammatory biomarkers (I), and classic AD biomarkers of Aβ and p-tau181 (C). Models incorporating inflammatory biomarkers assessed their contribution to improving baseline diagnostic classification and 1-year CMCD prediction.ResultsAt 1-year follow-up, 27.1% of participants experienced CMCD. Adding inflammatory biomarkers to models with D and A variables (DA model) improved classification of cognitively normal (CN) versus mild cognitive impairment (MCI) and CN versus Dementia (p < 0.001). Similarly, inflammatory markers enhanced classification in models including C (DAC model), for CN versus MCI (p < 0.01) and CN versus Dementia (p < 0.001). Predictive performance for CMCD was improved in individuals with MCI and dementia in both models (all p < 0.05). In addition, the DAI model outperformed the DAC model in predicting CMCD for MCI and Dementia groups (both p < 0.05).ConclusionsAddition of CSF inflammatory biomarkers to biomarkers of AD improves diagnostic accuracy of clinical disease stage at baseline and add incremental value to AD biomarkers for prediction of cognitive decline.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251335915"},"PeriodicalIF":3.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019542","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

Alpha-1-acid glycoprotein as a potential serum biomarker for cerebral amyloid angiopathy. α -1-酸性糖蛋白作为脑淀粉样血管病的潜在血清生物标志物。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-04-22 DOI: 10.1177/13872877251333802

Akisato Nishigaki, Hidehiro Ishikawa, Yamato Nishiguchi, Kei Tachibana, Natsuko Kato, Kana Matsuda, Yurie Mori, Hirofumi Matsuyama, Keita Matsuura, Yuichiro Ii, Hideaki Wakita, Shinji Oikawa, Hidekazu Tomimoto, Akihiro Shindo

{"title":"Alpha-1-acid glycoprotein as a potential serum biomarker for cerebral amyloid angiopathy.","authors":"Akisato Nishigaki, Hidehiro Ishikawa, Yamato Nishiguchi, Kei Tachibana, Natsuko Kato, Kana Matsuda, Yurie Mori, Hirofumi Matsuyama, Keita Matsuura, Yuichiro Ii, Hideaki Wakita, Shinji Oikawa, Hidekazu Tomimoto, Akihiro Shindo","doi":"10.1177/13872877251333802","DOIUrl":"https://doi.org/10.1177/13872877251333802","url":null,"abstract":"BackgroundCerebral amyloid angiopathy (CAA) is a form of cerebral small vessel disease (SVD) associated with Alzheimer's disease, intracerebral hemorrhage, and cognitive decline. Despite its clinical significance, no reliable serum biomarker exists for early diagnosis or monitoring of disease progression.ObjectiveThis study hypothesizes that α1-acid glycoprotein (α1-AGP) and other serum biomarkers can aid CAA diagnosis and assessment using gel-based mass spectrometry. A comparative analysis was performed to investigate associations between serum biomarkers and radiological scores.MethodsSerum proteins from individuals with probable or possible CAA (n = 10), classified using the modified Boston criteria, and age-matched controls (n = 10) were analyzed via two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS). Candidate proteins were validated using enzyme-linked immunosorbent assay (ELISA). Outcome measures included biomarker diagnostic accuracy, assessed by receiver operating characteristic (ROC) curve analysis, and correlations between α1-AGP levels and CAA-SVD scores.ResultsFour proteins-hemopexin, complement C3, complement C9, and α1-AGP-were significantly elevated, while apolipoprotein A-1 was reduced in the CAA group. ELISA confirmed higher α1-AGP levels in individuals with CAA (p < 0.0001). ROC analysis demonstrated that α1-AGP could indicate the presence of CAA with a sensitivity and specificity of 1.00 (95%CI: 1.000, 1.000). Additionally, α1-AGP levels correlated with the CAA-SVD score (R² = 0.783).Conclusionsα1-AGP may serve as a novel serum biomarker for CAA. Larger cohorts and external validation are required to substantiate these findings and determine their clinical relevance.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251333802"},"PeriodicalIF":3.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970306","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