Frontiers in Aging Neuroscience最新文献

{"title":"Effects of exercise interventions on cognitive function in patients with cognitive dysfunction: an umbrella review of meta-analyses.","authors":"Guangyao Sun, Xingyi Ding, Zhong Zheng, Hongtao Ma","doi":"10.3389/fnagi.2025.1553868","DOIUrl":"10.3389/fnagi.2025.1553868","url":null,"abstract":"<p><strong>Objective: </strong>This umbrella review assessed the quality, potential biases, and effects of exercise interventions on cognitive function in individuals with cognitive impairments.</p><p><strong>Methods: </strong>A comprehensive umbrella review of meta-analyses of randomized controlled trials (RCTs) was performed to evaluate the effects of exercise on cognitive function in individuals with cognitive impairments. Databases including Web of Science, PubMed, Embase, and the Cochrane Database of Systematic Reviews were searched. Outcomes were evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, classified as \"high,\" \"moderate,\" \"low,\" or \"very low\" quality.</p><p><strong>Results: </strong>A total of 55 meta-analyses were included, covering dementia, cognitive impairment, MCI, Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. Cognitive outcomes were assessed using scales like MMSE and MoCA. High-quality evidence supports Exergaming (SMD 0.69), Tai Chi (SMD 0.36), and traditional Chinese mind-body exercises (SMD 0.32) for improving MMSE and MoCA Score in MCI patients. For dementia, moderate-quality evidence shows resistance training (SMD 0.60) and Tai Chi (SMD 0.27) have positive effects. Aerobic exercise (MD 2.95) was more effective for AD, while mind-body exercises (MD 1.68) benefitted PD patients. Multi-component exercises (SMD 0.67) improved MMSE and MoCA scores in post-stroke cognitive impairment. For unspecified cognitive impairments, combining exercise with cognitive training and traditional Chinese exercises showed higher effectiveness. Due to small sample sizes, all findings were Class IV evidence, requiring further research.</p><p><strong>Conclusion: </strong>Moderate to high-quality evidence supports Exergaming, Tai Chi, and traditional Chinese exercises in improving cognitive function in MCI. For dementia, resistance training and Tai Chi are effective; for AD, aerobic exercise; for PD, mind-body exercises; and for post-stroke cognitive impairment, multi-component exercises are beneficial.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/view/CRD42024587635, identifier [CRD42024587635].</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1553868"},"PeriodicalIF":4.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198709","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":"Radiological features of gait phenotypes in patients with idiopathic normal pressure hydrocephalus.","authors":"Silvia Nicolosi, Massimiliano Todisco, Matteo Paoletti, Eduardo Caverzasi, Francesco Tarantino, Elena Ballante, Francesca Valentino, Roberta Zangaglia, Silvia Figini, Giuseppe Cosentino, Claudio Pacchetti, Anna Pichiecchio","doi":"10.3389/fnagi.2025.1554642","DOIUrl":"10.3389/fnagi.2025.1554642","url":null,"abstract":"<p><strong>Introduction: </strong>According to the higher-level gait disorder (HLGD) pattern, patients with idiopathic normal pressure hydrocephalus (iNPH) can be divided into two motor phenotypes; a disequilibrium (wide-based gait) subtype and a parkinsonian (locomotor) subtype. We aimed to understand the neuroimaging correlates of iNPH phenotyping into different gait patterns, by assessing specific radiological features and their correlations with clinical scores.</p><p><strong>Methods: </strong>We enrolled 86 probable iNPH patients (53 males; age range: 69-88 years), who underwent a comprehensive clinical assessment, including neuropsychological tests, and a conventional MRI scan. The cohort was subdivided into disequilibrium subtype (29 subjects) and parkinsonian subtype of HLGD (57 patients) based on gait evaluation. We compared the iNPH subtypes assessing differences in eight linear radiological indexes and their clinical correlates.</p><p><strong>Results: </strong>The Height of the third ventricle was the only radiological feature that differed between the two motor phenotypes (<i>p</i> < 0.05), being higher in the parkinsonian subtype and showing a trend of correlation with the motor score of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale and with the continence score of the iNPH Rating Scale. Among several clinical-radiological correlations, a reduced callosal angle correlated with the severity of motor and urinary symptoms (<i>p</i> < 0.05).</p><p><strong>Discussion: </strong>A greater height of the third ventricle possibly leading to a top-down compressive effect on the midbrain could be a neuroimaging marker of the parkinsonian phenotype of iNPH. The extensive correlations between linear radiological indices and clinical scales suggest a potential role for radiological features in clinical monitoring.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1554642"},"PeriodicalIF":4.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198712","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":"Effects of social support on cognitive frailty among the older adults in China: mediation of psychological resilience and moderated mediation of education.","authors":"Wenjuan Li, Yiwen Ma, Jinli Wei, Shanzheng Wu, Liangliang Cui, Chengchao Zhou","doi":"10.3389/fnagi.2025.1579485","DOIUrl":"10.3389/fnagi.2025.1579485","url":null,"abstract":"<p><strong>Objectives: </strong>Previous research has revealed a relationship between social support and cognitive frailty. However, the underlying mechanisms of this connection have still not been well explored. The study aimed to investigate the effect of social support on cognitive frailty, mediated by psychological resilience and to examine the moderated mediation effect of education.</p><p><strong>Methods: </strong>A total of 1,758 older adults aged 60 years and above were included in the analysis. A descriptive analysis was conducted to describe the sample characteristics. The moderated mediation models were examined using Mplus 8.3, in which the mediation variables was psychological resilience, and the moderation variable was education.</p><p><strong>Results: </strong>The prevalence of cognitive frailty among the older adults was 4.3%. Social support had a significant negative predictive effect on the cognitive frailty (<i>B</i> = -0.066, <i>p</i> < 0.01), the psychological resilience partially mediated the relationship between social support and cognitive frailty (<i>B</i> = -0.103, <i>p</i> < 0.001). Compared to illiterate, primary school (<i>B</i> = -0.184, <i>p</i> < 0.05), middle school (<i>B</i> = -0.244, <i>p</i> < 0.01) and high school or above (<i>B</i> = -0.315, <i>p</i> < 0.01) could regulate the relationship between social support and psychological resilience in older adults.</p><p><strong>Discussion: </strong>We present a conceptual model containing the mediated effects of psychological resilience and the moderated effect of education on the relationship between social support and cognitive frailty. We believe this model enhances understanding of these associations and could be instrumental in formulating intervention strategies to mitigate the incidence of cognitive frailty in older adults.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1579485"},"PeriodicalIF":4.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198710","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":"Evaluation of functional capacity and risk of depression in older patients with cancer as part of the comprehensive geriatric assessment.","authors":"Wiesław Fidecki, Katarzyna Przylepa, Marek Wytrzyszczewski, Mariusz Wysokiński","doi":"10.3389/fnagi.2025.1595336","DOIUrl":"10.3389/fnagi.2025.1595336","url":null,"abstract":"<p><strong>Background: </strong>The patient's somatic health status plays an important role in the factors predisposing to the development of depression. Any disease, especially a chronic one, often associated with pain, may contribute to the development of depression. The aim of the study was to assess the impact of functional capacity on the occurrence of depression among elderly cancer patients.</p><p><strong>Methods: </strong>The work used the diagnostic survey method and survey technique research tool consisted of standardized questionnaires: the Nurses' Observation Scale for Geriatric Patients (NOSGER), the Barthel scale, and the Geriatric Depression Scale (GDS). The authors conducted the study among 110 older adults patients with hospitalized at the Lublin Region Oncology Center in 2022.</p><p><strong>Results: </strong>When assessing patients using the NOSGER scale, the average result for the entire group was 45.98 ± 12.58 points. The examined people functioned best in terms of memory - average of 5.99 ± 1.32 points. The worst functioning was in the instrumental activities of everyday life - average 9.16 ± 3.61 points. In the assessment of the functional status using the Barthel scale, 54.54% of the respondents were classified as light. Based on the assessment of patients using the GDS scale, it was found that as many as 66.36% of the respondents did not experience symptoms of depression. The regression model showed that the NOSGER scale was a statistically significant variable explaining the geriatric depression scale score in the study group (<i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>Most respondents were fully functional. The surveyed seniors suffering from cancer had the greatest difficulties in the areas of moods and emotions as well as instrumental activities of everyday life. The occurrence of depression symptoms was found in over 30.00% of respondents. It is advisable to use research tools that take into account a wider range of aspects when assessing the impact of functional capacity on the possibility of depression among geriatric patients with cancer.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1595336"},"PeriodicalIF":4.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198711","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":"Diagnostic value of olfactory function testing for Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis.","authors":"Yuxuan Liu, Yunpeng Cao, Hongquan Wei","doi":"10.3389/fnagi.2025.1551939","DOIUrl":"10.3389/fnagi.2025.1551939","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is clinically classified into prodromal (asymptomatic), mild cognitive impairment (MCI) due to AD, and dementia due to AD. This study investigates the diagnostic value of olfactory function testing for AD and MCI.</p><p><strong>Methods: </strong>Systematic searches of PubMed, Web of Science, Cochrane, and EMBASE databases were conducted up to February 1, 2024. Methodological quality was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies. Effect sizes were combined using a random-effects model (DerSimonian-Laird method), and statistical analyses were conducted using STATA 15.1 and Meta-Disc 1.4 software.</p><p><strong>Results: </strong>Twenty-five studies with 13,611 participants were included. For diagnosing AD, combined sensitivity (SE) was 0.79 (95% CI: 0.71-0.85), specificity (SP) was 0.78 (95% CI: 0.69-0.84), and AUC was 0.85 (95% CI: 0.82-0.88). For MCI, SE was 0.67 (95% CI: 0.54-0.78), SP was 0.79 (95% CI: 0.71-0.86), and AUC was 0.81 (95% CI: 0.77-0.84). Combined SE and SP for diagnosing AD and MCI were 0.58 (95% CI: 0.46-0.68) and 0.88 (95% CI: 0.78-0.93), with an AUC of 0.78 (95% CI: 0.74-0.82). SE and SP for AD or MCI were 0.83 (95% CI: 0.36-0.98) and 0.94 (95% CI: 0.82-0.98), with an AUC of 0.96 (95% CI: 0.94-0.98).</p><p><strong>Conclusion: </strong>This systematic review and meta-analysis reveal that olfactory function testing, as a simple, non-invasive, and cost-effective assessment method, demonstrates high diagnostic efficacy in the early identification of AD and MCI, showing promising clinical application.</p><p><strong>Systematic review registration: </strong>CRD42024520871.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1551939"},"PeriodicalIF":4.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181473","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":"Predicting brain age for veterans with traumatic brain injuries and healthy controls: an exploratory analysis.","authors":"John P Coetzee, Xiaojian Kang, Victoria Liou-Johnson, Ines Luttenbacher, Srija Seenivasan, Elika Eshghi, Daya Grewal, Siddhi Shah, Frank Hillary, Emily L Dennis, Maheen M Adamson","doi":"10.3389/fnagi.2025.1472207","DOIUrl":"10.3389/fnagi.2025.1472207","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) is associated with increased dementia risk. This may be driven by underlying biological changes resulting from the injury. Machine learning algorithms can use structural MRIs to give a predicted brain age (pBA). When the estimated age is greater than the chronological age (CA), this is called the brain age gap (BAg). We analyzed this outcome in men and women with and without TBI.</p><p><strong>Objective: </strong>To determine whether factors that contribute to BAg, as estimated using the brainageR algorithm, differ between men and women who are US military Veterans with and without TBI.</p><p><strong>Methods: </strong>In an exploratory, hypothesis-generating analysis, we analyzed data from 85 TBI patients and 22 healthy controls (HCs). High-resolution T1W images were processed using FreeSurfer 7.0. pBAs were calculated from T1s. Differences between the two groups were tested using the Mann-Whitney U. Associations between the BAg and other factors were tested using partial Pearson's <i>r</i> within groups, controlling for CA, followed by construction of regression models.</p><p><strong>Results: </strong>After correcting for multiple comparisons, TBI patients and HCs differed on PCL score (higher for TBI patients) and cortical thickness (CT) in both hemispheres (higher for HCs). Among women TBI patients, BAg was correlated with pBA and hippocampal volume (HV), and among men TBI patients, BAg was correlated with pBA and CT. Among both men and women HCs, BAg was correlated only with CA. Four hierarchical regression models were constructed to predict BAg in each group, which controlled for CA and excluded pBA for multicollinearity. These models showed that HV predicted BAg among women with TBI, while CT predicted BAg among men with TBI, while only CA predicted BAg among HCs.</p><p><strong>Interpretation: </strong>These results offer tentative support to the view the factors associated with BAg among individuals with TBI differ from factors associated with BAg among HCs, and between men and women. Specifically, BAg among individuals with TBI is predicted by neuroanatomical factors, while among HCs it is predicted only by CA. This may reflect features of the algorithm, an underlying biological process, or both.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1472207"},"PeriodicalIF":4.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179890","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":"Mirodenafil improves cognitive function by reducing microglial activation and blood-brain barrier permeability in ApoE4 KI mice.","authors":"Yejin Park, Subin Moon, Harry Jung, Songyi Park, Ju Won Kim, Dan-Gyeong Song, Yong-Ho In, Sang Won Han, Jong-Hee Sohn, Chan Hee Lee","doi":"10.3389/fnagi.2025.1579411","DOIUrl":"10.3389/fnagi.2025.1579411","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) has significant public health concerns in the aging society. AD can compromise brain function and lead to severe neurological abnormalities associated with dementia. The human Apolipoprotein E (ApoE4) gene is a strong risk factor for AD. However, comprehensive analyses and improvements of mouse models expressing ApoE4 remain largely unexplored.</p><p><strong>Methods: </strong>ApoE4 knock-in (KI) mice were used to investigate the role of humanized ApoE4 in hippocampal histological changes and cognitive impairment. Cerebrovascular perfusion, blood-brain barrier (BBB) integrity, microgliosis, and amyloid-beta 42 (Aβ₄₂) accumulation were examined. Cognitive functions were assessed using the Morris water maze, Y-maze, and novel object recognition tests. Mirodenafil, a potent and selective phosphodiesterase 5 inhibitor (PDE5i), was orally administered to ApoE4 KI mice for 4 weeks. An <i>in vitro</i> BBB model and BV2 microglial cells were used to investigate endothelial permeability and inflammation.</p><p><strong>Results: </strong>ApoE4 KI mice exhibited not only reduced cerebrovascular perfusion and CLN-5 expression but also increased microgliosis and Aβ₄₂ accumulation in the hippocampus. These phenomena were accompanied by impaired cognitive functions. Mirodenafil administration reversed the histological and behavioral alterations induced by ApoE4 KI. <i>In vitro</i>, mirodenafil treatment mitigated Aβ₄₂-induced endothelial permeability and lipopolysaccharide-induced microglial inflammation.</p><p><strong>Discussion: </strong>These findings suggest that mirodenafil enhances cerebrovascular function, preserves BBB integrity, and mitigates neuroinflammation in ApoE4 KI mice, leading to cognitive improvement. PDE5 inhibition may serve as a promising therapeutic approach for addressing ApoE4-associated cerebrovascular and cognitive dysfunction.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1579411"},"PeriodicalIF":4.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179738","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":"Knowledge map of artificial intelligence in neurodegenerative diseases: a decade-long bibliometric and visualization study.","authors":"Junwei Huang, Shuqi Wang, Xuankai Liao, Danting Su, Rubing Lin, Tao Zhang, Long Zhao","doi":"10.3389/fnagi.2025.1586282","DOIUrl":"10.3389/fnagi.2025.1586282","url":null,"abstract":"<p><strong>Background: </strong>As the incidence of neurodegenerative diseases increases, the related AI research is getting more and more advanced. In this study, we analyze the literature in this field over the last decade through bibliometric and visualization methods with the aim of mining the prominent journals, institutions, authors, and countries in this field and analyzing the keywords in order to speculate on possible future research trends.</p><p><strong>Methods: </strong>Our study extracted 1,921 relevant publications spanning 2015-2025 from the Web of Science Core Collection database. We conducted comprehensive bibliometric analyses and knowledge mapping visualizations using established scientometric tools: CiteSpace and Bibliometrix.</p><p><strong>Results: </strong>A total of 1921 documents were included in the study, the number of publications in this field showed an overall increasing trend, and the average number of citations showed a downward trend since 2019. Among the journals, <i>Scientific Reports</i> had the highest number of publications. In addition, we identified 22 core journals. Institution wise, University of London has the highest participation. Among the authors, the highest number of publications is Benzinger, Tammie. The highest number of citations is Fingere Elizabeth. At the national level, the United States is number one in the world in terms of influence in this field, and China is ranked number two, both of which are well ahead of other countries and are major contributors to this field. The analysis of keywords showed the centrality of Alzheimer disease, machine learning, Parkinsons disease, and deep learning. All the studies were clustered based on keywords to get seven clusters: 0. immune infiltration; 1. Parkinsons disease; 2. multiple sclerosis; 3. mild cognitive impairment; 4. deep learning; 5. machine learning; 6. freesurfer; 7. scale. In addition, we also found the continuation of the trending topics, which are Parkinsons disease, deep learning, and machine learning.</p><p><strong>Conclusion: </strong>Based on the relationship between keywords and time, we speculate that there are four possible research trends: 1. Precision diagnosis with multimodal data fusion. 2. Pathological mechanism analysis and target discovery. 3. Interpretable AI and clinical translation. 4. Technology differentiation for subdivided diseases.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1586282"},"PeriodicalIF":4.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173312","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":"Identification and validation of pyroptosis-related genes in Alzheimer's disease based on multi-transcriptome and machine learning.","authors":"Yuntai Wang, Yilin Li, Lu Zhou, Yihuan Yuan, Chuanfei Liu, Zimeng Zeng, Yuanqi Chen, Qi He, Zhuoze Wu","doi":"10.3389/fnagi.2025.1568337","DOIUrl":"10.3389/fnagi.2025.1568337","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) progression is characterized by persistent neuroinflammation, where pyroptosis-an inflammatory programmed cell death mechanism-has emerged as a key pathological contributor. However, the molecular mechanisms through which pyroptosis-related genes (PRGs) drive AD pathogenesis remain incompletely elucidated.</p><p><strong>Methods: </strong>We integrated multiple transcriptomes of AD patients from the GEO database and analyzed the expression of PRGs in combined datasets. Machine learning algorithms and comprehensive bioinformatics analysis (including immune infiltration and receiver operating characteristic (ROC)) were applied to identify the hub genes. Additionally, we validated the expression patterns of these key genes using the expression data from AD mice and constructed potential regulatory networks through time series and correlation analysis.</p><p><strong>Results: </strong>We identified 91 PRGs in AD using the weighted gene co-expression network analysis (WGCNA) and differentially expressed genes analysis. By application of the protein-protein interaction and machine learning algorithms, seven pyroptosis feature genes (CHMP2A, EGFR, FOXP3, HSP90B1, MDH1, METTL3, and PKN2) were identified. Crucially, MDH1 and PKN2 demonstrated superior performance in terms of immune cell infiltration, ROC curves, and experimental validation. Furthermore, we constructed the long non-coding RNA and mRNA (lncRNA-mRNA) regulatory network of these characteristic genes using the gene expression profiles from AD mice at varying ages, revealing the potential regulatory mechanism in AD.</p><p><strong>Conclusion: </strong>This study provides the first comprehensive characterization of pyroptosis-related molecular signatures in AD. Seven hub genes were identified, with particular emphasis on MDH1 and PKN2. Their superior performances were validated through comprehensive bioinformatic analysis in both patient and mouse transcriptomes, as well as the experimental data. Our findings establish foundational insights into pyroptosis mechanisms in AD that may inform novel treatment strategies targeting neuroinflammatory pathways.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1568337"},"PeriodicalIF":4.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173344","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":"Iron responsive elements mRNA regulate Alzheimer's amyloid precursor protein translation through iron sensing.","authors":"Mateen A Khan","doi":"10.3389/fnagi.2025.1483913","DOIUrl":"10.3389/fnagi.2025.1483913","url":null,"abstract":"<p><p>Iron responsive element (IREs) mRNA and iron regulatory proteins (IRPs) regulate iron homeostasis. 5'-untranslated region motifs of APP IREs fold into RNA stem loops bind to IRP to control translation. Through the 5'-UTR APP IREs, iron overload accelerated the translation of the Alzheimer's amyloid precursor protein (APP). The protein synthesis activator eIF4F and the protein synthesis repressor IRP1 are the two types of proteins that IREs bind. Iron regulates the competitive binding of eIF4F and IRP1 to IRE. Iron causes the IRE and eIF4F to associate with one other, causing the dissociation of IRPs and altered translation. In order to control IRE-modulated expression of APP, messenger RNAs are becoming attractive targets for the development of small molecule therapeutics. Many mRNA interference strategies target the 2-D RNA structure, but messenger RNAs like rRNAs and tRNAs can fold into complicated, three-dimensional structures that add another level of complexity. IREs family is one of the few known 3-D mRNA regulatory elements. In this review, I present IREs structural and functional characteristics. For iron metabolism, the mRNAs encoding the proteins are controlled by this family of similar base sequences. Iron has a similar way of controlling the expression of Alzheimer's APP as ferritin IRE RNA in their 5ÚTR. Further, iron mis regulation by IRPs can be investigated and contrasted using measurements of expression levels of APP, amyloid-<i>β</i> and tau formation. Accordingly, IRE-modulated APP expression in Alzheimer's disease has great therapeutic potential through targeting mRNA structures.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1483913"},"PeriodicalIF":4.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173309","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}