Frontiers in Aging Neuroscience最新文献

{"title":"Association of modified dementia risk score with cerebrospinal fluid biomarkers and cognition in adults without dementia","authors":"Qiong-Yao Li, Yan Fu, Xin-Jing Cui, Zuo-teng Wang, Lan Tan","doi":"10.3389/fnagi.2024.1339163","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1339163","url":null,"abstract":"This study aimed to investigate the cognitive profile and prospective cognitive changes in non-demented adults with elevated Modified Dementia Risk Scores (MDRS), while also exploring the potential relationship between these associations and cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) pathology and neuroinflammation.Within the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database, 994 participants without dementia were assessed on MDRS, CSF biomarkers and cognition. We examined the associations of the MDRS with CSF biomarkers and cognitive scores using linear regressions. Causal mediation analyses were conducted to analyze the associations among MDRS, brain pathologies, and cognition. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) study was used to validate the mediation effects and to investigate the longitudinal association between MDRS and cognitive decline.The results revealed that higher MDRS were linked to poorer cognitive performance (Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) and increases in CSF levels of phosphorylated tau (P-tau, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001), total tau (T-tau, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001), P-tau/Aβ42 ratio (Model 1: PFDR = 0.023; Model 2: PFDR = 0.028), T-tau/Aβ42 ratio (Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) and soluble triggering receptor expressed on myeloid cells 2 (sTrem2, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) in the CABLE study. The impact of MDRS on cognition was partially mediated by neuroinflammation and tau pathology. These mediation effects were replicated in the ADNI study. Baseline MDRS were significantly associated with future cognitive decline, as indicated by lower scores on the Mini-Mental State Examination (MMSE, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001), ADNI composite memory score (ADNI-MEM, Model 1: PFDR = 0.005; Model 2: PFDR < 0.001), ADNI composite executive function score (ADNI-EF, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001), and higher score on the Alzheimer’s Disease Assessment Scale (ADAS13, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001).The findings of this study revealed significant associations between MDRS and cognitive decline, suggesting a potential role of tau pathology and neuroinflammation in the link between MDRS and poorer cognitive performance in individuals without dementia. Consequently, the MDRS holds promise as a tool for targeted preventive interventions in individuals at high risk of cognitive impairment.","PeriodicalId":503985,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"2 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic link between KIF1A mutations and amyotrophic lateral sclerosis: evidence from whole-exome sequencing","authors":"Wei Zheng, Ji He, Lu Chen, Weiyi Yu, Nan Zhang, Xiaoxuan Liu, D. Fan","doi":"10.3389/fnagi.2024.1421841","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1421841","url":null,"abstract":"Genetics have been shown to have a substantial impact on amyotrophic lateral sclerosis (ALS). The ALS process involves defects in axonal transport and cytoskeletal dynamics. It has been identified that KIF1A, responsible for encoding a kinesin-3 motor protein that carries synaptic vesicles, is considered a genetic predisposing factor for ALS.The analysis of whole-exome sequencing data from 1,068 patients was conducted to examine the genetic link between ALS and KIF1A. For patients with KIF1A gene mutations and a family history, we extended the analysis to their families and reanalyzed them using Sanger sequencing for cosegregation analysis.In our cohort, the KIF1A mutation frequency was 1.31% (14/1,068). Thirteen nonsynonymous variants were detected in 14 ALS patients. Consistent with the connection between KIF1A and ALS, the missense mutation p.A1083T (c.3247G>A) was shown to cosegregate with disease. The mutations related to ALS in our study were primarily located in the cargo-binding region at the C-terminal, as opposed to the mutations of motor domain at the N-terminal of KIF1A which were linked to hereditary peripheral neuropathy and spastic paraplegia. We observed high clinical heterogeneity in ALS patients with missense mutations in the KIF1A gene. KIF5A is a more frequent determinant of ALS in the European population, while KIF1A accounts for a similar proportion of ALS in both the European and Chinese populations.Our investigation revealed that mutations in the C-terminus of KIF1A could increase the risk of ALS, support the pathogenic role of KIF1A in ALS and expand the phenotypic and genetic spectrum of KIF1A-related ALS.","PeriodicalId":503985,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"94 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141647179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of Immune cells in Alzheimer's disease: a bidirectional Mendelian randomization study","authors":"Erdong Zhang, Tingting Chen, Yanqin Chen, Chenxiang Long, Ling Tao, Xiangchun Shen, Fengqiu Dai","doi":"10.3389/fnagi.2024.1433691","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1433691","url":null,"abstract":"Alzheimer's disease (AD) is a leading cause of dementia, characterized by the accumulation of amyloid-beta (Aβ) and hyperphosphorylated tau proteins, leading to neuroinflammation and neuronal damage. The role of the immune system in AD pathogenesis is increasingly recognized, prompting an exploration of the causal relationship between immune cells and AD by using Mendelian randomization (MR) approaches.Utilizing genome-wide association study (GWAS) data from European cohorts, we conducted an MR study to investigate the causal links between immune cell phenotypes and AD. We selected single nucleotide polymorphisms (SNPs) associated with immune cell traits at a genome-wide significance threshold and applied various MR methods, including MR Egger, Weighted median, and inverse variance weighted analysis, to assess the causality between 731 immune phenotypes and AD.Our MR analysis identified 15 immune cell types with significant causal relationships to AD pathogenesis. Notably, the absolute count of CD28−CD4−CD8− T cells and the expression of HLA DR on B cells were linked to a protective effect against AD, while 13 other immune phenotypes were identified as contributing to the risk factors for the disease. The causal effects of AD on immunophenotypic traits are predominantly negative, implying that AD may impair the functionality of immune cells. Validation through independent datasets, such as FinnGen and GCST90027158, confirmed the causal association between six specific immune cells and AD.This comprehensive MR study elucidates the intricate network of causal relationships between diverse immunophenotypic traits and AD, providing novel insights into the immunopathogenesis of AD. The findings suggest potential immunological targets that could be leveraged for early diagnosis, disease monitoring, and therapeutic intervention.","PeriodicalId":503985,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"106 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141647443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bibliometric analysis of neuroinflammation and Alzheimer’s disease","authors":"Wenxian Sun, Jin Gong, Shaoqi Li, Pin Wang, Xiaodong Han, Chang Xu, Heya Luan, Ruina Li, Boye Wen, Cuibai Wei","doi":"10.3389/fnagi.2024.1423139","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1423139","url":null,"abstract":"Alzheimer’s disease (AD) is the predominant cause of dementia on a global scale, significantly impacting the health of the elderly population. The pathogenesis of AD is closely linked to neuroinflammation. The present study employs a bibliometric analysis to examine research pertaining to neuroinflammation and AD within the last decade, with the objective of providing a comprehensive overview of the current research profile, hotspots and trends.This research conducted a comprehensive review of publications within the Science Citation Index Expanded of the Web of Science Core Collection Database spanning the years 2014 to 2024. Bibliometric analyses were performed using VOSviewer (version 1.6.19) and CiteSpace (version 6.3.R1) software to visualize data on countries, institutions, authors, journals, keywords, and references.A total of 3,833 publications on neuroinflammation and AD were included from January 2014 to January 2024. Publications were mainly from the United States and China. Zetterberg, Henrik emerged as the author with the highest publication output, while Edison, Paul was identified as the most cited author. The most productive journal was Journal of Alzheimers Disease, and the most co-cited was Journal of Neuroinflammation. Research hotspot focused on microglia, mouse models, oxidative stress, and amyloid-beta through keyword analysis. Additionally, keywords such as blood–brain barrier and tau protein exhibited prolonged citation bursts from 2022 to 2024.This study provides a comprehensive review of the last 10 years of research on neuroinflammation and AD, including the number and impact of research findings, research hotspots, and future trends. The quantity of publications in this field is increasing, mainly in the United States and China, and there is a need to further strengthen close cooperation with different countries and institutions worldwide. Presently, research hotspots are primarily concentrated on microglia, with a focus on inhibiting their pro-inflammatory responses and promoting their anti-inflammatory functions as a potential direction for future investigations.","PeriodicalId":503985,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"54 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141648601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The causal effects of intelligence and fluid intelligence on Parkinson’s disease: a Mendelian randomization study","authors":"C. Jing, Xiaojiao Zhong, Xuli Min, Hao Xu","doi":"10.3389/fnagi.2024.1388795","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1388795","url":null,"abstract":"Parkinson’s disease (PD) is a chronic neurodegenerative disease that affects the central nervous system, primarily the motor nervous system, and occurs most often in older adults. A large number of studies have shown that high intelligence leads to an increased risk of PD. However, whether there is a causal relationship between intelligence on PD has not yet been reported.In this study, Mendelian randomization (MR) analysis was performed with intelligence (ebi-a-GCST006250) and fluid intelligence score (ukb-b-5238) as exposure factors and PD (ieu-b-7) as an outcome, which the datasets were mined from the IEU OpenGWAS database. MR analysis was performed through 3 methods [MR Egger, weighted median, inverse variance weighted (IVW)], of which IVW was the primary method. In addition, the reliability of the results of the MR analysis was assessed via the heterogeneity test, the horizontal polytropy test, and Leave-One-Out (LOO). Finally, based on gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, the genes corresponding to intelligence and fluid intelligence score related to SNPs were enriched for functional features and pathways.The results of MR analysis suggested that elevated intelligence indicators can increase the risk of PD [p = 0.015, Odd Ratio (OR) = 1.316]. Meanwhile, fluid intelligence score was causally associated with the PD (p = 0.035), which was a risk factor (OR = 1.142). The reliability of the results of MR analysis was demonstrated by sensitivity analysis. Finally, the results of GO enrichment analysis for 87 genes corresponding to intelligence related SNPs mainly included regulation of synapse organization, developmental cell growth, etc. These genes were enriched in the synaptic vessel cycle, polycomb expressive complex in KEGG. Similarly, 44 genes corresponding to SNPs associated with fluid intelligence score were used for enrichment analysis. Based on the GO database, these genes were mainly enriched in regulation of developmental growth, negative regulation of neuron projection development, etc. In KEGG, 44 genes corresponding to SNPs associated with fluid intelligence score were enriched in signaling pathways including Alzheimer’s disease, the cellular senescence, etc.The causal relationships between intelligence and fluid intelligence scores, and PD were demonstrated through MR analysis, providing an important reference and evidence for the study of PD.","PeriodicalId":503985,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"108 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141105837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving associative memory in younger and older adults with unitization: evidence from meta-analysis and behavioral studies","authors":"Zejun Liu, Yujuan Wang, Yajun Zhu, Jing Yuan, Wei Liu","doi":"10.3389/fnagi.2024.1389957","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1389957","url":null,"abstract":"The finding that familiarity can support associative memory by unitizing the to -be-learned items into a novel representation has been widely accepted, but its effects on overall performance of associative memory and recollection are still controversial.The current study aims to elucidate these discrepancies by identifying potential moderating factors through a combined approach of meta-analysis and behavioral experiment.Results consistently showed that changes in the level of unitization and age groups were two important moderators. Specifically, unitization enhanced younger and older adults’ associative memory and its supporting processes (i.e., familiarity and recollection) when the level of unitization between studied and rearranged pairs was changed. However, when this level remained constant, unitization exhibited no impact on associative memory and familiarity in younger adults, but showed an enhanced effect in older adults. Furthermore, results revealed a marked group difference between younger and older adults in associative memory when the unitization level of noncompound words remained unaltered. Upon breaking this condition, the group difference was reduced by enhancing familiarity or recollection.These findings not only clarify some of the inconsistencies in the literature concerning the impact of unitization on associative memory, but also suggest that unitization is a beneficial strategy for reducing group difference in associative memory, with its effectiveness varying according to the level of unitization changes.","PeriodicalId":503985,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"18 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141104599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of soluble TREM2 with Alzheimer’s disease and mild cognitive impairment: a systematic review and meta-analysis","authors":"Ruiqi Wang, Yi-jun Zhan, Wen-Qing Zhu, Qianwen Yang, Jian Pei","doi":"10.3389/fnagi.2024.1407980","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1407980","url":null,"abstract":"Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is a potential neuroinflammatory biomarker linked to the pathogenesis of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Previous studies have produced inconsistent results regarding sTREM2 levels in various clinical stages of AD. This study aims to establish the correlation between sTREM2 levels and AD progression through a meta-analysis of sTREM2 levels in cerebrospinal fluid (CSF) and blood.Comprehensive searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Library to identify observational studies reporting CSF and blood sTREM2 levels in AD patients, MCI patients, and healthy controls. A random effects meta-analysis was used to calculate the standardized mean difference (SMD) and 95% confidence intervals (CIs).Thirty-six observational studies involving 3,016 AD patients, 3,533 MCI patients, and 4,510 healthy controls were included. CSF sTREM2 levels were significantly higher in both the AD [SMD = 0.28, 95% CI (0.15, 0.41)] and MCI groups [SMD = 0.30, 95% CI (0.13, 0.47)] compared to the healthy control group. However, no significant differences in expression were detected between the AD and MCI groups [SMD = 0.09, 95% CI (−0.09, 0.26)]. Furthermore, increased plasma sTREM2 levels were associated with a higher risk of AD [SMD = 0.42, 95% CI (0.01, 0.83)].CSF sTREM2 levels are positively associated with an increased risk of AD and MCI. Plasma sTREM2 levels were notably higher in the AD group than in the control group and may serve as a promising biomarker for diagnosing AD. However, sTREM2 levels are not effective for distinguishing between different disease stages of AD. Further investigations are needed to explore the longitudinal changes in sTREM2 levels, particularly plasma sTREM2 levels, during AD progression.https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024514593","PeriodicalId":503985,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"62 40","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141110437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P-hydroxybenzaldehyde protects Caenorhabditis elegans from oxidative stress and β-amyloid toxicity","authors":"Xingzhi Yu, Jie Tao, Tian Xiao, Xiaohua Duan","doi":"10.3389/fnagi.2024.1414956","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1414956","url":null,"abstract":"Gastrodia elata is the dried tuber of the orchid Gastrodia elata Bl. It is considered a food consisting of a source of precious medicinal herbs, whose chemical composition is relatively rich. Gastrodia elata and its extracted fractions have been shown to have neuroprotective effects. P-hydroxybenzaldehyde (p-HBA), as one of the main active components of Gastrodia elata, has anti-inflammatory, antioxidative stress, and cerebral protective effects, which has potential for the treatment of Alzheimer’s disease (AD). The aim of this study was to verify the role of p-HBA in AD treatment and to investigate its mechanism of action in depth based using the Caenorhabditis elegans (C. elegans) model.In this study, we used paralysis, lifespan, behavioral and antistress experiments to investigate the effects of p-HBA on AD and aging. Furthermore, we performed reactive oxygen species (ROS) assay, thioflavin S staining, RNA-seq analysis, qPCR validation, PCR Array, and GFP reporter gene worm experiment to determine the anti-AD effects of p-HBA, as well as in-depth studies on its mechanisms.p-HBA was able to delay paralysis, improve mobility and resistance to stress, and delay aging in the AD nematode model. Further mechanistic studies showed that ROS and lipofuscin levels, Aβ aggregation, and toxicity were reduced after p-HBA treatment, suggesting that p-HBA ameliorated Aβ-induced toxicity by enhancing antioxidant and anti-aging activity and inhibiting Aβ aggregation. p-HBA had a therapeutic effect on AD by improving stress resistance, as indicated by the down-regulation of NLP-29 and UCR-11 expression and up-regulation of PQN-75 and LYS-3 expression. In addition, the gene microarray showed that p-HBA treatment played a positive role in genes related to AD, anti-aging, ribosomal protein pathway, and glucose metabolism, which were collectively involved in the anti-AD mechanism of p-HBA. Finally, we also found that p-HBA promoted nuclear localization of DAF-16 and increased the expression of SKN-1, SOD-3, and GST-4, which contributed significantly to inhibition of Aβ toxicity and enhancement of antioxidative stress.Our work suggests that p-HBA has some antioxidant and anti-aging activities. It may be a viable candidate for the treatment and prevention of Alzheimer’s disease.","PeriodicalId":503985,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"62 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141110553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between physical frailty and cortical structure in middle-aged and elderly people: a Mendelian randomization study","authors":"Xin Zhang, Zhen Wang, Jing Zou, Le Zhang, Jinghua Ning, Bei Jiang, Yi Liang, Yuzhe Zhang","doi":"10.3389/fnagi.2024.1395553","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1395553","url":null,"abstract":"Physical weakness is associated with cortical structures, but the exact causes remain to be investigated. Therefore, we utilized Mendelian randomization (MR) analysis to uncover the underlying connection between frailty and cortical structures.The Genome-Wide Association Study (GWAS) on frailty pooled data from publicly available sources such as the UK Biobank and included five indicators of frailty: weakness, walking speed, weight loss, physical activity, and exhaustion. GWAS data on cerebral cortical structure were obtained from the ENIGMA consortium, and we assessed the causal relationship between hereditary frailty and cortical surface area (SA) or cortical thickness (TH). Inverse variance weighting (IVW) was used as the primary estimate, and heterogeneity and multidimensionality were monitored by MR-PRESSO to detect outliers. Additionally, MR-Egger, Cochran’s Q test, and weighted median were employed.At the aggregate level, there was no causal relationship between frailty and cortical thickness or surface area. At the regional level, frailty was associated with the thickness of the middle temporal lobe, parahippocampus, rostral middle frontal lobe, lower parietal lobe, anterior cingulate gyrus, upper temporal lobe, lateral orbital frontal cortex, pericardial surface area, rostral middle frontal lobe, upper temporal lobe, rostral anterior cingulate gyrus, lower parietal lobe, and upper parietal lobe. These results were nominally significant, and sensitivity analyses did not detect any multidirectionality or heterogeneity, suggesting that the results of our analyses are reliable.The results of our analyses suggest a potential causal relationship between somatic weakness and multiple regions of cortical structure. However, the specific mechanisms of influence remain to be investigated. Preliminary results from our analysis suggest that the effects of physical frailty on cortical structures are influenced by various factors related to frailty exposure. This relationship has been documented, and it is therefore both feasible and meaningful to build on existing research to explore the clinical significance of the relationship.","PeriodicalId":503985,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"46 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141108947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation subsequent to mild iron excess differentially alters regional brain iron metabolism, oxidation and neuroinflammation status in mice","authors":"Azhaar Ashraf, Manal Aljuhani, Chantal J. Hubens, Jérôme Jeandriens, Harold G. Parkes, K. Geraki, A. Mahmood, Amy H. Herlihy, Po-Wah So","doi":"10.3389/fnagi.2024.1393351","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1393351","url":null,"abstract":"Iron dyshomeostasis and neuroinflammation, characteristic features of the aged brain, and exacerbated in neurodegenerative disease, may induce oxidative stress-mediated neurodegeneration. In this study, the effects of potential priming with mild systemic iron injections on subsequent lipopolysaccharide (LPS)-induced inflammation in adult C57Bl/6J mice were examined. After cognitive testing, regional brain tissues were dissected for iron (metal) measurements by total reflection X-ray fluorescence and synchrotron radiation X-Ray fluorescence-based elemental mapping; and iron regulatory, ferroptosis-related, and glia-specific protein analysis, and lipid peroxidation by western blotting. Microglial morphology and astrogliosis were assessed by immunohistochemistry. Iron only treatment enhanced cognitive performance on the novel object location task compared with iron priming and subsequent LPS-induced inflammation. LPS-induced inflammation, with or without iron treatment, attenuated hippocampal heme oxygenase-1 and augmented 4-hydroxynonenal levels. Conversely, in the cortex, elevated ferritin light chain and xCT (light chain of System Xc−) were observed in response to LPS-induced inflammation, without and with iron-priming. Increased microglial branch/process lengths and astrocyte immunoreactivity were also increased by combined iron and LPS in both the hippocampus and cortex. Here, we demonstrate iron priming and subsequent LPS-induced inflammation led to iron dyshomeostasis, compromised antioxidant function, increased lipid peroxidation and altered neuroinflammatory state in a brain region-dependent manner.","PeriodicalId":503985,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"113 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141116066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}