Frontiers in Aging Neuroscience最新文献

{"title":"Frontiers | Alteration of cGAS-STING signaling pathway components in the mouse cortex and hippocampus during healthy brain aging","authors":"Sergio Passarella, Shananthan Kethiswaran, Karina Brandes, I-Chin Tsai, Kristin Cebulski, Andrea Kröger, Daniela C. Dieterich, Peter Landgraf","doi":"10.3389/fnagi.2024.1429005","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1429005","url":null,"abstract":"The cGAS-STING pathway is a pivotal element of the innate immune system, recognizing cytosolic DNA to initiate the production of type I interferons and pro-inflammatory cytokines. This study investigates the alterations of the cGAS-STING signaling components in the cortex and hippocampus of mice aged 24 and 108 weeks. In the cortex of old mice, an increase in the dsDNA sensor protein cGAS and its product 2′3′-cGAMP was observed, without corresponding activation of downstream signaling, suggesting an uncoupling of cGAS activity from STING activation. This phenomenon may be attributed to increased dsDNA concentrations in the EC neurons, potentially arising from nuclear DNA damage. Contrastingly, the hippocampus did not exhibit increased cGAS activity with aging, but there was a notable elevation in STING levels, particularly in microglia, neurons and astrocytes. This increase in STING did not correlate with enhanced IRF3 activation, indicating that brain inflammation induced by the cGAS-STING pathway may manifest extremely late in the aging process. Furthermore, we highlight the role of autophagy and its interplay with the cGAS-STING pathway, with evidence of autophagy dysfunction in aged hippocampal neurons leading to STING accumulation. These findings underscore the complexity of the cGAS-STING pathway’s involvement in brain aging, with regional variations in activity and potential implications for neurodegenerative diseases.","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141867616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of endogenous estrogens, plasma Alzheimer’s disease biomarkers, and APOE4 carrier status on regional brain volumes in postmenopausal women","authors":"Katrina A. Wugalter, Rachel A. Schroeder, Rebecca C. Thurston, Minjie Wu, Howard J. Aizenstein, Ann D. Cohen, M. Ilyas Kamboh, Thomas K. Karikari, Carol A. Derby, Pauline M. Maki","doi":"10.3389/fnagi.2024.1426070","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1426070","url":null,"abstract":"BackgroundWomen carrying the <jats:italic>APOE4</jats:italic> allele are at greater risk of developing Alzheimer’s disease (AD) from ages 65–75 years compared to men. To better understand the elevated risk conferred by <jats:italic>APOE4</jats:italic> carrier status among midlife women, we investigated the separate and interactive associations of endogenous estrogens, plasma AD biomarkers, and <jats:italic>APOE4</jats:italic> carrier status on regional brain volumes in a sample of late midlife postmenopausal women.MethodsParticipants were enrolled in MsBrain, a cohort study of postmenopausal women (<jats:italic>n</jats:italic> = 171, mean age = 59.4 years, mean MoCA score = 26.9; race = 83.2% white, <jats:italic>APOE4</jats:italic> carriers = 40). Serum estrone (E1) and estradiol (E2) levels were assessed using liquid chromatography–tandem mass spectrometry. APOE genotype was determined using TaqMan SNP genotyping assays. Plasma AD biomarkers were measured using single molecule array technology. Cortical volume was measured and segmented by FreeSurfer software using individual T1w MPRAGE images. Multiple linear regression models were conducted to determine whether separate and interactive associations between endogenous estrogen levels, plasma AD biomarkers (Aβ42/Aβ40, Aβ42/p-tau181), and <jats:italic>APOE4</jats:italic> carrier status predict regional brain volume (21 regions per hemisphere, selected <jats:italic>a priori</jats:italic>); and, whether significant interactive associations between estrogens and AD biomarkers on brain volume differed by <jats:italic>APOE4</jats:italic> carrier status.ResultsThere was no main effect of <jats:italic>APOE4</jats:italic> carrier status on regional brain volumes, endogenous estrogen levels, or plasma AD biomarkers. Estrogens did not associate with regional brain volumes, except for positive associations with left caudal middle frontal gyrus and fusiform volumes. The interactive association of estrogens and <jats:italic>APOE4</jats:italic> carrier status on brain volume was not significant for any region. The interactive association of estrogens and plasma AD biomarkers predicted brain volume of several regions. Higher E1 and E2 were more strongly associated with greater regional brain volumes among women with a poorer AD biomarker profile (lower Aβ42/40, lower Aβ42/p-tau181 ratios). In <jats:italic>APOE4</jats:italic>-stratified analyses, these interactions were driven by non-<jats:italic>APOE4</jats:italic> carriers.ConclusionWe demonstrate that the brain volumes of postmenopausal women with poorer AD biomarker profiles benefit most from higher endogenous estrogen levels. These findings are driven by non-<jats:italic>APOE4</jats:italic> carriers, suggesting that <jats:italic>APOE4</jats:italic> carriers may be insensitive to the favorable effects of estrogens on brain volume in the postmenopause.","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141570052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Neuroinflammation and cognitive impairment.","authors":"Juan Li, Yang Wang, Kun Xiong, Chengjin Gao","doi":"10.3389/fnagi.2024.1453772","DOIUrl":"10.3389/fnagi.2024.1453772","url":null,"abstract":"","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751502","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":"Potential increased propofol sensitivity in cognitively impaired elderly: a controlled, double-blind study","authors":"Huiting Zhuge, Yu Zhou, Yimin Qiu, Xiaojing Huang","doi":"10.3389/fnagi.2024.1410181","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1410181","url":null,"abstract":"BackgroundCognitive impairment in the elderly may lead to potential increased sensitivity to anesthetic agents targeting receptors associated with cognition. This study aimed to explore the effect of cognitive status on propofol consumption during surgery in elderly patients.MethodsSixty elderly patients scheduled for laparoscopic radical prostatectomy were allocated to either a cognitively normal [CogN, Montreal Cognitive Assessment (MoCA) score ≥26] or cognitively impaired (CogI, MoCA &amp;lt;26) group. Propofol was administered via target-controlled infusion to maintain a bispectral index (BIS) between 55–65 during surgery. Propofol consumption was recorded at three time points: T1 (abolished eyelash reflex), T2 (BIS = 50), T3 (extubation). BIS values at eyelash reflex abolition were also recorded. Postoperative MoCA, Visual Analogue Scale (VAS) scores, and remifentanil/sufentanil consumption were assessed.ResultsBIS values before induction were similar between CogN and CogI groups. However, at eyelash reflex abolition, BIS was significantly higher in CogI than CogN (mean ± SD: 65.3 ± 7.2 vs. 61.1 ± 6.8, <jats:italic>p</jats:italic> = 0.031). Propofol requirement to reach BIS 50 was lower in CogI vs. CogN (1.24 ± 0.19 mg/kg vs. 1.46 ± 0.12 mg/kg, <jats:italic>p</jats:italic> = 0.003). Postoperative MoCA, VAS scores, and remifentanil/sufentanil consumption did not differ significantly between groups.ConclusionCompared to cognitively intact elderly, those with cognitive impairment exhibited higher BIS at eyelash reflex abolition and required lower propofol doses to achieve the same BIS level, suggesting increased propofol sensitivity. Cognitive status may impact anesthetic medication requirements in the elderly.","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141570051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring research hotspots and emerging trends in neuroimaging of vascular cognitive impairment: a bibliometric and visualized analysis","authors":"Fangyuan Xu, Ziliang Dai, Wendong Zhang, Yu Ye, Fan Dai, Peijia Hu, Hongliang Cheng","doi":"10.3389/fnagi.2024.1408336","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1408336","url":null,"abstract":"BackgroundVascular cognitive impairment (VCI) manifests in memory impairment, mental slowness, executive dysfunction, behavioral changes, and visuospatial abnormalities, significantly compromising the quality of daily life for patients and causing inconvenience to caregivers. Neuroimaging serves as a crucial approach to evaluating the extent, location, and type of vascular lesions in patients suspected of VCI. Nevertheless, there is still a lack of comprehensive bibliometric analysis to discern the research status and emerging trends concerning VCI neuroimaging.ObjectiveThis study endeavors to explore the collaboration relationships of authors, countries, and institutions, as well as the research hotspots and frontiers of VCI neuroimaging by conducting a bibliometric analysis.MethodsWe performed a comprehensive retrieval within the Core Collection of Web of Science, spanning from 2000 to 2023. After screening the included literature, CiteSpace and VOSviewer were utilized for a visualized analysis aimed at identifying the most prolific author, institution, and journal, as well as extracting valuable information from the analysis of references.ResultsA total of 1,024 publications were included in this study, comprising 919 articles and 105 reviews. Through the analysis of keywords and references, the research hotspots involve the relationship between neuroimaging of cerebral small vessel disease (CSVD) and VCI, the diagnosis of VCI, and neuroimaging methods pertinent to VCI. Moreover, potential future research directions encompass CSVD, functional and structural connectivity, neuroimaging biomarkers, and lacunar stroke.ConclusionThe research in VCI neuroimaging is constantly developing, and we hope to provide insights and references for future studies by delving into the research hotspots and frontiers within this field.","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141570053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward the development of a sporadic model of Alzheimer's disease: comparing pathologies between humanized APP and the familial J20 mouse models","authors":"Peggy Rentsch, Kiruthika Ganesan, Alexander Langdon, Lyndsey M. Konen, Bryce Vissel","doi":"10.3389/fnagi.2024.1421900","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1421900","url":null,"abstract":"BackgroundFinding successful therapies for individuals with Alzheimer's disease (AD) remains an ongoing challenge. One contributing factor is that the mouse models commonly used in preclinical research primarily mimic the familial form of AD, whereas the vast majority of human cases are sporadic. Accordingly, for a sporadic mouse model of AD, incorporating the multifactorial aspects of the disease is of utmost importance.MethodsIn the current study, we exposed humanized Aβ knock-in mice (hAβ-KI) to weekly low-dose lipopolysaccharide (LPS) injections until 24 weeks of age and compared the development of AD pathologies to the familial AD mouse model known as the J20 mice.ResultsAt the early time point of 24 weeks, hAβ-KI mice and J20 mice exhibited spatial memory impairments in the Barnes maze. Strikingly, both hAβ-KI mice and J20 mice showed significant loss of dendritic spines when compared to WT controls, despite the absence of Aβ plaques in hAβ-KI mice at 24 weeks of age. Glial cell numbers remained unchanged in hAβ-KI mice compared to WT, and LPS exposure in hAβ-KI mice did not result in memory deficits and failed to exacerbate any other examined AD pathology.ConclusionThe study highlights the potential of hAβ-KI mice as a model for sporadic AD, demonstrating early cognitive deficits and synaptic alterations despite no evidence of Aβ plaque formation. These findings underscore the importance of considering multifactorial influences in sporadic AD pathogenesis and the need for innovative models to advance our understanding and treatment strategies for this complex disease.","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141570055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontiers | Identification of deregulated lncRNAs in Alzheimer’s disease: an integrated gene co-expression network analysis of hippocampus and fusiform gyrus RNA-seq datasets","authors":"Ermes Filomena, Ernesto Picardi, Apollonia Tullo, Graziano Pesole, Anna Maria D’Erchia","doi":"10.3389/fnagi.2024.1437278","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1437278","url":null,"abstract":"IntroductionThe deregulation of lncRNAs expression has been associated with neuronal damage in Alzheimer’s disease (AD), but how or whether they can influence its onset is still unknown. We investigated 2 RNA-seq datasets consisting, respectively, of the hippocampal and fusiform gyrus transcriptomic profile of AD patients, matched with non-demented controls.MethodsWe performed a differential expression analysis, a gene correlation network analysis (WGCNA) and a pathway enrichment analysis of two RNA-seq datasets.ResultsWe found deregulated lncRNAs in common between hippocampus and fusiform gyrus and deregulated gene groups associated to functional pathways related to neurotransmission and memory consolidation. lncRNAs, co-expressed with known AD-related coding genes, were identified from the prioritized modules of both brain regions.DiscussionWe found common deregulated lncRNAs in the AD hippocampus and fusiform gyrus, that could be considered common signatures of AD pathogenesis, providing an important source of information for understanding the molecular changes of AD.","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141718414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Occlusion dysfunction and Alzheimer’s disease: Mendelian randomization study","authors":"Qing Wang, Wenyu Zhen, Rui Hu, Zifei Wang, Yuqiang Sun, Wansu Sun, Chunxia Huang, Jianguang Xu, Hengguo Zhang","doi":"10.3389/fnagi.2024.1423322","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1423322","url":null,"abstract":"AimOcclusion dysfunction (OD) is increasingly linked to Alzheimer’s disease (AD). This study aimed to elucidate the causal relationship between OD and AD using Mendelian randomization (MR) analysis.Materials and methodsGenome-wide association study (GWAS) meta-analysis data obtained from FinnGen, IEU Open GWAS, and UK Biobank (UKBB) was represented as instrumental variables. We validated the causal relationship between periodontal disease (PD), loose teeth (PD &amp;amp; occlusion dysfunction), dentures restoration (occlusion recovery), and AD.ResultsAccording to the MR analysis, PD and AD have no direct causal relationship (P = 0.395, IVW). However, loose teeth significantly increased the risk of AD progression (P = 0.017, IVW, OR = 187.3567, 95%CI = 2.54E+00−1.38E+04). These findings were further supported by the negative causal relationship between dentures restoration and AD (P = 0.015, IVW, OR = 0.0234, 95%CI = 1.13E-03−0.485).ConclusionThe occlusion dysfunction can ultimately induce Alzheimer’s disease. Occlusion function was a potentially protective factor for maintaining neurological health.","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141547662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum: Glutamatergic and GABAergic neurons in the preoptic area of the hypothalamus play key roles in menopausal hot flashes.","authors":"Yanrong Sun, Hanfei Wang, Wenjuan Wang, Jiali Lu, Jinglin Zhang, Xiaofeng Luo, Liju Luan, Ke Wang, Jing Jia, Junhao Yan, Lihua Qin","doi":"10.3389/fnagi.2024.1072608","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1072608","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fnagi.2022.993955.].</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723387","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":"A glimpse into the future: revealing the key factors for survival in cognitively impaired patients","authors":"Libing Wei, Dikang Pan, Sensen Wu, Hui Wang, Jingyu Wang, Lianrui Guo, Yongquan Gu","doi":"10.3389/fnagi.2024.1376693","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1376693","url":null,"abstract":"BackgroundDrawing on prospective data from the National Health and Nutrition Examination Survey (NHANES), our goal was to construct and validate a 5-year survival prediction model for individuals with cognitive impairment (CI).MethodsThis study entailed a prospective cohort design utilizing information from the 2011–2014 NHANES dataset, encompassing individuals aged 40 years or older, with updated mortality status as of December 31, 2019. Predictive models within the derivation and validation cohorts were assessed using logistic proportional risk regression, column-line plots, and least absolute shrinkage and selection operator (LASSO) binomial regression models.ResultsThe study enrolled a total of 1,439 participants (677 men, mean age 69.75 ± 6.71 years), with the derivation and validation cohorts consisting of 1,007 (538 men) and 432 (239 men) individuals, respectively. The 5-year mortality rate stood at 16.12% (<jats:italic>n</jats:italic> = 232). We devised a 5-item column-line graphical model incorporating age, race, stroke, cardiovascular disease (CVD), and blood urea nitrogen (BUN). The model exhibited an area under the curve (AUC) of 0.772 with satisfactory calibration. Internal validation demonstrated that the column-line graph model displayed strong discrimination, yielding an AUC of 0.733, and exhibited good calibration.ConclusionTo sum up, our study successfully developed and internally validated a 5-item nomogram integrating age, race, stroke, cardiovascular disease, and blood urea nitrogen. This nomogram exhibited robust predictive performance for 5-year mortality in individuals with CI, offering a valuable tool for prognostic evaluation and personalized care planning.","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141547659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}