Frontiers in Aging Neuroscience最新文献

{"title":"Mapping the current trends and hotspots of extracellular vesicles in Alzheimer's disease: a bibliometric analysis.","authors":"Xiaolian Xing, Hongwei Liu, Minheng Zhang, Yang Li","doi":"10.3389/fnagi.2024.1485750","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1485750","url":null,"abstract":"<p><strong>Background: </strong>Extracellular vesicles (EVs) have garnered significant attention in Alzheimer's disease (AD) research over the past decade, largely due to their potential in diagnostics and therapeutics. Although the investigation of EVs in AD is a relatively recent endeavor, a comprehensive bibliometric analysis of this rapidly growing field has yet to be conducted.</p><p><strong>Methods: </strong>This study aims to elucidate and synthesize the relationship between EVs and AD, offering critical insights to guide future research and expand therapeutic possibilities. Over the past 10-15 years, substantial progress has been made in this domain. Through bibliometric techniques, this analysis assesses research performance by examining scientific publications and metrics, including productivity indicators, impact measurements, data mining, and visualization tools.</p><p><strong>Results: </strong>A total of 602 publications were analyzed using various online platforms for bibliometric analysis. Notably, the number of publications began to increase rapidly in 2018, with China and the United States emerging as leaders in this research area. The National Institute on Aging produced the highest number of publications among institutions. The <i>Journal of Molecular Sciences</i> and the <i>Journal of Biological Chemistry</i> were the most prolific and most frequently cited journals, respectively. Among individual contributors, Dimitrios Kapogiannis was identified as the most productive author, while Edward J. Goetzl was the most co-cited. The most prevalent keywords included \"neurodegenerative diseases,\" \"exosomes,\" \"blood biomarkers,\" \"amyloid beta,\" \"microglia,\" and \"tau protein.\" Current research hotspots involve microRNA dysregulation, oxidative stress, carboxyl-terminal fragments, small EVs, and mesenchymal stem cell-derived EVs, indicating key areas for future research.</p><p><strong>Conclusion: </strong>Research on microRNA dysregulation, oxidative stress, carboxyl-terminal fragments, small EVs, and mesenchymal stem cell-derived EVs represents a critical frontier in the study of Alzheimer's disease. The role of EV-mediated neuroinflammation in AD is a focal point of ongoing investigation and will likely shape future developments in the field.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1485750"},"PeriodicalIF":4.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between metallic implants and stroke in US adults from NHANES 2015-2023 a cross-sectional study.","authors":"Kai Wu, Liang Pang, Pingping Su, Cunxian Lv","doi":"10.3389/fnagi.2024.1505645","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1505645","url":null,"abstract":"<p><strong>Objective: </strong>Metal implants play a vital role in orthopedic treatment and are widely used in fracture repair, joint replacement and spinal surgery. Although these implants often contain key elements such as chromium (Cr), their potential health effects, particularly their association with stroke risk, have not been fully elucidated. This study aimed to evaluate the association between metallic implants and stroke.</p><p><strong>Methods: </strong>Using data from the 2015 to 2023 National Health and Nutrition Examination Survey (NHANES), we conducted a cross-sectional analysis of 12,337 US adults, in which 3,699 participants reported having metal implants and 8,638 without. Implant-like.</p><p><strong>Results: </strong>Through logistic regression analysis, we revealed a significant positive association between metallic implants and stroke risk (adjusted OR = 1.458, 95%CI (1.130, 1.881), <i>p</i> = 0.004). Further stratified analysis found that this positive association was more significant among older and less physically active participants.</p><p><strong>Conclusion: </strong>Findings suggest that metallic implants may be associated with an increased risk of stroke, but given the inherent limitations of cross-sectional studies, this study cannot establish causality.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1505645"},"PeriodicalIF":4.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidimensional relationships between sensory perception and cognitive aging.","authors":"Lakshmi Kannan, Esteban Sebastian Lelo de Larrea-Mancera, Marcello Maniglia, Mariya M Vodyanyk, Frederick J Gallun, Susanne M Jaeggi, Aaron R Seitz","doi":"10.3389/fnagi.2024.1484494","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1484494","url":null,"abstract":"<p><p>A growing literature suggests that declines in sensory/perceptual systems predate cognitive declines in aging, and furthermore, they are highly predictive for developing Alzheimer's disease and Alzheimer's related dementias (ADRD). While vision, hearing, olfaction, and vestibular function have each been shown to be related to ADRD, their causal relations to cognitive declines, how they interact with each other remains to be clarified. Currently, there is substantial debate whether sensory/perceptual systems that fail early in disease progression are causal in their contributions to cognitive load and/or social isolation or are simply coincident declines due to aging. At the same time, substantial declines in any of these senses requires compensation, can strain other neural processes and impact activities of daily living, including social engagement, quality of life, and the risk of falls. In this perspective piece, we review literature that illustrates the different relationships between sensory/perceptual systems, cognitive aging and ADRD. We suggest that broadly administered and precise assessment of sensory/perceptual functions could facilitate early detection of ADRD and pave the way for intervention strategies that could help reduce the multifaceted risk of developing ADRD and to improve everyday functioning as people age.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1484494"},"PeriodicalIF":4.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between Alzheimer's disease pathologic products and age and a pathologic product-based diagnostic model for Alzheimer's disease.","authors":"Weizhe Zhen, Yu Wang, Hongjun Zhen, Weihe Zhang, Wen Shao, Yu Sun, Yanan Qiao, Shuhong Jia, Zhi Zhou, Yuye Wang, Leian Chen, Jiali Zhang, Dantao Peng","doi":"10.3389/fnagi.2024.1513930","DOIUrl":"10.3389/fnagi.2024.1513930","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) has a major negative impact on people's quality of life, life, and health. More research is needed to determine the relationship between age and the pathologic products associated with AD. Meanwhile, the construction of an early diagnostic model of AD, which is mainly characterized by pathological products, is very important for the diagnosis and treatment of AD.</p><p><strong>Method: </strong>We collected clinical study data from September 2005 to August 2024 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Using correlation analysis method like cor function, we analyzed the pathology products (t-Tau, p-Tau, and Aβ proteins), age, gender, and Minimum Mental State Examination (MMSE) scores in the ADNI data. Next, we investigated the relationship between pathologic products and age in the AD and non-AD groups using linear regression. Ultimately, we used these features to build a diagnostic model for AD.</p><p><strong>Results: </strong>A total of 1,255 individuals were included in the study (mean [SD] age, 73.27 [7.26] years; 691male [55.1%]; 564 female [44.9%]). The results of the correlation analysis showed that the correlations between pathologic products and age were, in descending order, Tau (Corr=0.75), p-Tau (Corr=0.71), and Aβ (Corr=0.54). In the AD group, t-Tau protein showed a tendency to decrease with age, but it was not statistically significant. p-Tau protein levels similarly decreased with age and its decrease was statistically significant. In contrast to Tau protein, in the AD group, Aβ levels increased progressively with age. In the non-AD group, the trend of pathologic product levels with age was consistently opposite to that of the AD group. We finally screened the optimal AD diagnostic model (AUC=0.959) based on the results of correlation analysis and by using the Xgboost algorithm and SVM algorithm.</p><p><strong>Conclusion: </strong>In a novel finding, we observed that Tau protein and Aβ had opposite trends with age in both the AD and non-AD groups. The linear regression curves of the AD and non-AD groups had completely opposite trends. Through a machine learning approach, we constructed an AD diagnostic model with excellent performance based on the selected features.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1513930"},"PeriodicalIF":4.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiorespiratory fitness, hippocampal subfield morphology, and episodic memory in older adults.","authors":"Hayley S Ripperger, Rebecca G Reed, Chaeryon Kang, Alina Lesnovskaya, Sarah L Aghjayan, Haiqing Huang, Lu Wan, Bradley P Sutton, Lauren Oberlin, Audrey M Collins, Jeffrey M Burns, Eric D Vidoni, Arthur F Kramer, Edward McAuley, Charles H Hillman, George A Grove, John M Jakicic, Kirk I Erickson","doi":"10.3389/fnagi.2024.1466328","DOIUrl":"10.3389/fnagi.2024.1466328","url":null,"abstract":"<p><strong>Objective: </strong>Age-related hippocampal atrophy is associated with memory loss in older adults, and certain hippocampal subfields are more vulnerable to age-related atrophy than others. Cardiorespiratory fitness (CRF) may be an important protective factor for preserving hippocampal volume, but little is known about how CRF relates to the volume of specific hippocampal subfields, and whether associations between CRF and hippocampal subfield volumes are related to episodic memory performance. To address these gaps, the current study evaluates the associations among baseline CRF, hippocampal subfield volumes, and episodic memory performance in cognitively unimpaired older adults from the Investigating Gains in Neurocognition Trial of Exercise (IGNITE) (NCT02875301).</p><p><strong>Methods: </strong>Participants (<i>N</i> = 601, ages 65-80, 72% female) completed assessments including a graded exercise test measuring peak oxygen comsumption (VO_2peak) to assess CRF, cognitive testing, and high-resolution magnetic resonance imaging of the hippocampus processed with Automated Segmentation of Hippocampal Subfields (ASHS). Separate linear regression models examined whether CRF was associated with hippocampal subfield volumes and whether those assocations were moderated by age or sex. Mediation models examined whether hippocampal volumes statistically mediated the relationship between CRF and episodic memory performance. Covariates included age, sex, years of education, body mass index, estimated intracranial volume, and study site.</p><p><strong>Results: </strong>Higher CRF was significantly associated with greater total left (<i>B</i> = 5.82, <i>p</i> = 0.039) and total right (<i>B</i> = 7.64, <i>p</i> = 0.006) hippocampal volume, as well as greater left CA2 (<i>B</i> = 0.14, <i>p</i> = 0.022) and dentate gyrus (DG; <i>B</i> = 2.34, <i>p</i> = 0.031) volume, and greater right CA1 (<i>B</i> = 3.99, <i>p</i> = 0.011), CA2 (<i>B</i> = 0.15, <i>p</i> = 0.002), and subiculum (<i>B</i> = 1.56, <i>p</i> = 0.004) volume. Sex significantly moderated left DG volume (<i>B</i> = -4.26, <i>p</i> = 0.017), such that the association was positive and significant only for males. Total left hippocampal volume [indirect effect = 0.002, 95% CI (0.0002, 0.00), <i>p</i> = 0.027] and right subiculum volume [indirect effect = 0.002, 95% CI (0.0007, 0.01), <i>p</i> = 0.006] statistically mediated the relationship between CRF and episodic memory performance.</p><p><strong>Discussion: </strong>While higher CRF was significantly associated with greater total hippocampal volume, CRF was not associated with all underlying subfield volumes. Our results further demonstrate the relevance of the associations between CRF and hippocampal volume for episodic memory performance. Finally, our results suggest that the regionally-specific effects of aging and Alzheimer's disease on hippocampal subfields could be mitigated by maintaining higher CRF in older adulthood.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1466328"},"PeriodicalIF":4.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attenuated afferent inhibition correlated with impaired gait performance in Parkinson's disease patients with freezing of gait.","authors":"Puyuan Wen, Hong Zhu, Zaichao Liu, Amin Chang, Xianwen Chen","doi":"10.3389/fnagi.2024.1458005","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1458005","url":null,"abstract":"<p><strong>Background: </strong>The neural mechanisms underlying freezing of gait (FOG) in Parkinson's disease (PD) have not been completely comprehended. Sensory-motor integration dysfunction was proposed as one of the contributing factors. Here, we investigated short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI), and analyzed their association with gait performance in FOG PD patients, to further validate the role of sensorimotor integration in the occurrence of FOG in PD.</p><p><strong>Methods: </strong>Twenty-five levodopa responsive-FOG PD patients (LR-FOG), fifteen levodopa unresponsive-FOG PD patients (LUR-FOG), twenty-eight PD patients without FOG (NO-FOG PD) and twenty-two healthy controls (HC) were included in the study. Clinical features such as PD motor symptoms, FOG severity and cognitive abilities were evaluated using clinical scales in subjects with PD. All participants underwent paired associative stimulation (PAS) to evaluate SAI and LAI in addition to regular input-output curve by transcranial magnetic stimulation. The performances of gait were assessed using a portable gait analyzing system in 10-meter timed Up and Go task. The correlations between the gait spatiotemporal parameters or the scores of FOG scale and the magnitudes of SAI or LAI were analyzed.</p><p><strong>Results: </strong>Compared to HC and NO-FOG PD patients, SAI was decreased in FOG PD subgroups. LAI was also reduced in both LR-FOG PD and LUR-FOG PD in relative to HC; however, only LUR-FOG PD showed significant reduction of LAI in comparison to NO-FOG PD group. FOG PD patients showed poorer gait performance compared to HC and NO-FOG PD group. The reduction of SAI and LAI were correlated with the impaired gait spatiotemporal parameters or scores of FOG scale in PD with FOG.</p><p><strong>Conclusion: </strong>The SAI and LAI were attenuated in PD patients with FOG, and the reduction of SAI or LAI were correlated to disturbed gait performance, indicating that sensory-motor integration dysfunction played a role in the development of FOG in PD.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1458005"},"PeriodicalIF":4.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating music therapy and video games in cognitive interventions: innovative applications of closed-loop EEG.","authors":"Ying Wang, Kexin Zhang, Hao Yu, Xianglong Wan, Tiange Liu, Danyang Li, Dingna Duan, Xueguang Xie, Dong Wen","doi":"10.3389/fnagi.2024.1498821","DOIUrl":"10.3389/fnagi.2024.1498821","url":null,"abstract":"","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1498821"},"PeriodicalIF":4.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted plasma metabolomics reveals potential biomarkers of the elderly with mild cognitive impairment in Qingdao rural area.","authors":"Yuchi Meng, Murong Cheng, Hongyan Qu, Zhenxue Song, Ling Zhang, Yuanjun Zeng, Dongfeng Zhang, Suyun Li","doi":"10.3389/fnagi.2024.1511437","DOIUrl":"10.3389/fnagi.2024.1511437","url":null,"abstract":"<p><strong>Introduction: </strong>Previous research has suggested a link between the onset of Alzheimer's disease (AD) and metabolic disorder; however, the findings have been inconsistent. To date, the majority of metabolomics studies have focused on AD, resulting in a relative paucity of research on early-stage conditions such as mild cognitive impairment (MCI) underexplored. In this study, we employed a comprehensive platform for the early screening of individuals with MCI using high-throughput targeted metabolomics.</p><p><strong>Method: </strong>We included 171 participants including 124 individuals with MCI and 47 healthy subjects. Univariate statistical analysis was conducted using <i>t</i>-tests or Wilcoxon rank-sum tests, with <i>p</i>-values corrected by the Benjamini-Hochberg method. The screening criteria were set at FDR < 0.05 and fold change (FC) > 1.5 or < 0.67. Multivariate analysis was performed using orthogonal partial least squares discriminant analysis (OPLS-DA), where differential metabolites were identified based on variable influence on projection (VIP) scores (VIP > 1 and FDR < 0.05). Random forest analysis was used to further evaluate the ability of the metabolic data to distinguish effectively between the two groups.</p><p><strong>Results: </strong>A total of 14 differential metabolites were identified, leading to the discovery of a biomarker panel consisting of three plasma metabolites including uric acid, pyruvic acid and isolithocholic acid that effectively distinguished MCI patients from healthy subjects.</p><p><strong>Discussion: </strong>These findings have provided a comprehensive metabolic profile, offering valuable insights into the early prediction and understanding of the pathogenic processes underlying MCI. This study holds the potential for advancing early detection and intervention strategies for MCI.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1511437"},"PeriodicalIF":4.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apolipoprotein E dysfunction in Alzheimer's disease: a study on miRNA regulation, glial markers, and amyloid pathology.","authors":"Printha Wijesinghe, Hao Ran Li, Zhengyuan Ai, Matthew Campbell, Si Xuan Chen, Jeanne Xi, Wellington Pham, Joanne A Matsubara","doi":"10.3389/fnagi.2024.1495615","DOIUrl":"10.3389/fnagi.2024.1495615","url":null,"abstract":"<p><strong>Introduction: </strong>Apolipoprotein E (ApoE) plays a crucial role in lipid homeostasis, predominantly expressed in astrocytes and to a lesser extent in microglia within the central nervous system (CNS). While the <i>APOE4</i> allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD), its precise role in AD pathogenesis remains elusive. <i>Apoe</i>-knockout (<i>Apoe</i>-ko) mice, mice expressing human <i>APOE4</i>, and human <i>APOE4</i> carriers exhibit similar deficits in lipid metabolism, cognitive and behavioral functions, and neurodegeneration. The retina, as part of the CNS, has been studied to investigate the underlying mechanisms of AD, including neuroinflammation, amyloid aggregation, and neurodegeneration. This study explores ApoE's role in AD by analyzing brain and eye samples from <i>Apoe</i>-ko mice, focusing on identifying potential retinal biomarkers associated with ApoE dysfunction.</p><p><strong>Methods: </strong>We compared female <i>Apoe</i>-ko mice on a regular diet to age-matched C57BL/6J controls at 3 and 9 months. Our investigations included microRNAs (miRNAs), their target messenger RNAs (mRNAs), and selected protein markers, including astroglial (Gfap), microglial/macrophage (Iba1 and Trem2) markers, and amyloid precursor protein (APP)/amyloid-β (Aβ) peptides implicated in AD pathogenesis. We also examined female <i>Apoe</i>-ko mice on a high-fat diet versus a regular diet at 9 months for differential miRNA and mRNA expressions.</p><p><strong>Results: </strong>Our findings demonstrated that miRNA levels were generally lower in 3-month-old <i>Apoe</i>-ko mice but increased in 9-month-old mice across five distinct brain regions, as well as in eye tissue and tear fluid. A high-fat diet further enhanced miRNA dysregulation in brain and eye tissues, but not in tear fluid. Target mRNAs were generally higher in the neocortex-hippocampus and eye tissue of 3-month-old <i>Apoe</i>-ko mice but decreased with age, except for glial cell mRNAs like <i>Gfap</i> and <i>Aif1</i>. Protein analysis revealed elevated Gfap expression, and increased APP/Aβ peptide accumulation in the neocortex-hippocampus, including brain endothelial cells at the meninges, as well as in the retina of 9-month-old <i>Apoe</i>-ko mice. These findings highlight ApoE's pivotal role in AD, demonstrating its impact on inflammatory and amyloidogenic/angiogenic miRNA expression, glial homeostasis, and APP/Aβ peptide clearance. The observed upregulation of proinflammatory miR-146a and anti-amyloidogenic/angiogenic miR-15a in 9-month-old <i>Apoe</i>-ko mice suggests their potential as tear-based biomarkers for ApoE dysfunction.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1495615"},"PeriodicalIF":4.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modifying reaction time tasks parameters in the automated IntelliCage identifies heightened impulsivity and impaired attention in the 3xTg-AD model of Alzheimer's disease.","authors":"Jessica M Judd, Wendy Winslow, Ian McDonough, Faizan Mistry, Ramon Velazquez","doi":"10.3389/fnagi.2024.1466415","DOIUrl":"10.3389/fnagi.2024.1466415","url":null,"abstract":"<p><strong>Background: </strong>The 3xTg-AD transgenic mouse model of Alzheimer's disease (AD) is an important tool to investigate the relationship between development of pathological amyloid-β (Aβ) and tau, neuroinflammation, and cognitive impairments. Traditional behavioral tasks assessing aspects of learning and memory, such as mazes requiring spatial navigation, unfortunately suffer from several shortcomings, including the stress of human handling and not probing species-typical behavior. The automated IntelliCage system was developed to circumvent such issues by testing mice in a social environment while measuring multiple aspects of cognition. Water consumption can serve as a primary motivator for task engagement. Once animals adapt to the cage and can access water, mice can be subjected to operant tasks. Each of the four corners of a cage contains doors to manipulate access to water, visual LED cues, and a valve allowing administration of an air puff. Previously, we detected significant impairments in 3xTg-AD mice in the IntelliCage, however a high failure rate and genotypical differences in water motivation were observed.</p><p><strong>Methods: </strong>Here, we implemented an IntelliCage paradigm where mice underwent progressively more difficult reaction time tasks to assess attention and impulsivity, behaviors mediated by the prefrontal cortex. Mice were placed in the IntelliCage at 11.5 months of age, which corresponds with the presence of widespread pathology.</p><p><strong>Results: </strong>As the difficulty of the reaction time tasks increased, 3xTg-AD mice exhibited lower percent Correct Responses than NonTg. When implementing varying pre-cue durations, where animals are required to wait between the initiation of the trial and the LED turning on (which then requires a nose-poke to access water), 3xTg-AD mice prematurely nose-poked on trials requiring a longer delay before a second nose poke would allow water access, demonstrating heightened impulsivity. The presence of soluble and insoluble fractions of cortical Aβ40 and 42, and phosphorylated tau epitopes threonine 181 and serine 396 confirmed the presence of neuropathological hallmarks in 3xTg-AD mice.</p><p><strong>Conclusion: </strong>Together, this study describes a novel protocol that overcomes motivational differences and detects attention and impulsivity deficits in 3xTg-AD mice utilizing the IntelliCage.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1466415"},"PeriodicalIF":4.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}