Aging brain最新文献

Tau aggregation induces cell death in iPSC-derived neurons Tau 聚集诱导 iPSC 衍生神经元的细胞死亡

IF 1.7

Aging brain Pub Date : 2025-01-01 DOI: 10.1016/j.nbas.2025.100136

Hirokazu Tanabe , Sumihiro Maeda , Etsuko Sano , Norio Sakai , Setsu Endoh-Yamagami , Hideyuki Okano

{"title":"Tau aggregation induces cell death in iPSC-derived neurons","authors":"Hirokazu Tanabe , Sumihiro Maeda , Etsuko Sano , Norio Sakai , Setsu Endoh-Yamagami , Hideyuki Okano","doi":"10.1016/j.nbas.2025.100136","DOIUrl":"10.1016/j.nbas.2025.100136","url":null,"abstract":"<div><div>Abnormal accumulation of tau proteins in the brain is a hallmark of neurodegenerative diseases such as Alzheimer’s disease and is closely linked with neuronal cell death. Tau accumulation is a prominent therapeutic target for Alzheimer’s disease, since tau accumulation correlates well with the disease progression, and tau-targeting drugs hold potentials to halt the disease progression. Given the differential response of human and mouse neuronal cells, there is a critical need for a human cellular platform to quickly screen for tau-related neurodegenerative disease therapeutics. However, inducing rapid, tau-dependent neuronal cell death in human models remains challenging. In this study, we established a human cellular model capable of inducing tau aggregation-dependent neuronal cell death within two weeks via tau overexpression. Additionally, we demonstrated the neuroprotective efficacy of known tau-targeting compounds within this system. These findings suggest that our cellular model recapitulates the molecular pathogenesis of tau-induced neurodegeneration and could serve as a valuable platform for drug screening in tauopathies.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"7 ","pages":"Article 100136"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816765","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}

引用次数: 0

TOMM40 may mediate GFAP, neurofilament light Protein, pTau181, and brain morphometry in aging TOMM40可能在衰老过程中介导GFAP、神经丝轻蛋白、pTau181和脑形态计量学。

IF 1.7

Aging brain Pub Date : 2025-01-01 DOI: 10.1016/j.nbas.2024.100134

Robyn A. Honea , Heather Wilkins , Suzanne L. Hunt , Paul J. Kueck , Jeffrey M. Burns , Russell H. Swerdlow , Jill K. Morris

{"title":"TOMM40 may mediate GFAP, neurofilament light Protein, pTau181, and brain morphometry in aging","authors":"Robyn A. Honea , Heather Wilkins , Suzanne L. Hunt , Paul J. Kueck , Jeffrey M. Burns , Russell H. Swerdlow , Jill K. Morris","doi":"10.1016/j.nbas.2024.100134","DOIUrl":"10.1016/j.nbas.2024.100134","url":null,"abstract":"<div><div>A growing amount of data has implicated the <em>TOMM40</em> gene in the risk for Alzheimer’s disease (AD), neurodegeneration, and accelerated aging. No studies have investigated the relationship of <em>TOMM40</em> rs2075650 (‘650<em>)</em> on the structural complexity of the brain or plasma markers of neurodegeneration. We used a comprehensive approach to quantify the impact of <em>TOMM40</em> ‘650 on brain morphology and multiple cortical attributes in cognitively unimpaired (CU) individuals. We also tested whether the presence of the risk allele, G, of <em>TOMM40</em> ‘650 was associated with plasma markers of amyloid, tau, and neurodegeneration and if there were interactions with age and sex, controlling for the effects of <em>APOE</em> ε4. We found that the <em>TOMM40</em> ‘650 G-allele was associated with decreased sulcal depth, increased gyrification index, and decreased gray matter volume. NfL, GFAP, and pTau181 had independent and age-associated increases in individuals with a G-allele. Our data suggest that <em>TOMM40</em> ‘650 is associated with aging-related plasma biomarkers and brain structure variation in temporal-limbic circuits.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"7 ","pages":"Article 100134"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

No sex differences in the association between regional brain structure abnormalities and cognitive functioning in a geriatric memory clinic population 在老年记忆临床人群中，区域脑结构异常和认知功能之间的关联没有性别差异

IF 1.7

Aging brain Pub Date : 2025-01-01 DOI: 10.1016/j.nbas.2025.100137

A. Lamé , E.G. Thomas , S.A.J. van de Schraaf , C. Groot , C.H. Sudre , F. Barkhof , M. Muller , R. Ossenkoppele , H.F.M. Rhodius-Meester

{"title":"No sex differences in the association between regional brain structure abnormalities and cognitive functioning in a geriatric memory clinic population","authors":"A. Lamé , E.G. Thomas , S.A.J. van de Schraaf , C. Groot , C.H. Sudre , F. Barkhof , M. Muller , R. Ossenkoppele , H.F.M. Rhodius-Meester","doi":"10.1016/j.nbas.2025.100137","DOIUrl":"10.1016/j.nbas.2025.100137","url":null,"abstract":"<div><div>Differences between men and women in cognitive impairment and neurodegeneration are not yet well understood. Although sex differences in brain structure abnormalities, including white matter hyperintensities (WMH) and grey matter (GM) atrophy, have been associated with cognitive decline in the ageing population, the evidence is limited and inconclusive. Therefore, we explored sex differences in brain structure abnormalities and in the association between brain structure abnormalities and cognitive functioning. We analyzed global and regional volumetric measures of WMH and GM of 475 patients visiting an academic geriatric memory clinic in the Netherlands with multiple linear regression analyses. For both global and regional WMH and GM, we found no sex differences in brain structure abnormalities. We also found no interaction of sex on the association between brain structure abnormalities and cognitive functioning. We reflect on using a binary classification of men and women based on sex in this study, which might overlook individual differences and does not elucidate gender-related factors that influence health and risk of pathology. Future studies should focus on exploring the relationship between sex and gender on brain structure and cognitive functioning beyond this binary model, by including more data on social context, more diverse populations and using intersectional approaches.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"7 ","pages":"Article 100137"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902418","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}

引用次数: 0

Complex span measures of working memory do not mediate the effects of age on the P3 and N400 ERPs 工作记忆的复杂广度测量不介导年龄对P3和N400 erp的影响

IF 1.7

Aging brain Pub Date : 2025-01-01 DOI: 10.1016/j.nbas.2025.100140

Jasmin Joshi, Chandlyr M. Denaro, Alan A. Hartley, Catherine L. Reed

{"title":"Complex span measures of working memory do not mediate the effects of age on the P3 and N400 ERPs","authors":"Jasmin Joshi, Chandlyr M. Denaro, Alan A. Hartley, Catherine L. Reed","doi":"10.1016/j.nbas.2025.100140","DOIUrl":"10.1016/j.nbas.2025.100140","url":null,"abstract":"<div><div>Working memory (WM), the temporary maintenance of a limited amount of information in an accessible state, is required for the performance of many tasks. Studies have shown that WM demands are related to the neural processing of tasks requiring attention: Age affects the ERP components associated with WM context updating processes in the visual oddball task (P3) and semantic processing in the word-pair judgment task (N400). This study investigated whether WM capacity measured by complex span tasks mediates the effects of age on these ERPs. Younger adults (YA, n = 44, ages 18–23 yr) and older adults (OA, n = 41, ages 69–89 yr) completed operation, reading, and symmetry complex span tasks and two ERP tasks (P3/visual oddball; N400/word-pair judgment). Results showed age-related differences for all complex span tests. Principal components analysis of these tests showed a single factor for both groups, so a combined WM capacity factor score was created. Regressions of age group and WM factor score on P3 and N400 amplitudes and latencies showed that OAs had relatively lower amplitudes and longer latencies. However complex span was not related to P3 or N400 amplitudes or latencies and that result was the same for younger and older adults; that is, complex span did not mediate the age effects. WM processes indexed by the P3 and N400 components appear to be different from those elicited by complex span tasks. Attentional control processes of WM influence oddball and semantic judgement tasks more than storage components.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"7 ","pages":"Article 100140"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922898","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}

引用次数: 0

Selenium deficiency negatively affects survival and integrity of human hippocampal progenitor cells 缺硒对人海马祖细胞的存活和完整性有负面影响

IF 1.7

Aging brain Pub Date : 2025-01-01 DOI: 10.1016/j.nbas.2025.100138

Sahand Farmand, Emaan Ahmed, Hadisa Azizi Zawar, Sandrine Thuret

{"title":"Selenium deficiency negatively affects survival and integrity of human hippocampal progenitor cells","authors":"Sahand Farmand, Emaan Ahmed, Hadisa Azizi Zawar, Sandrine Thuret","doi":"10.1016/j.nbas.2025.100138","DOIUrl":"10.1016/j.nbas.2025.100138","url":null,"abstract":"<div><div>Selenium has been shown to be a key regulatory element in the health, survival and proliferation of neural stem and progenitor cells, with various studies underlining its anti-aging properties. However, most of this knowledge is derived from rodent models, leaving its effects on human hippocampal progenitor cells unclear. In this study, we utilized a human hippocampal progenitor cell (HPC) line to examine the effects of varying concentrations of sodium selenite, an inorganic form of selenium (0 µM, 0.1 µM, 0.23 µM, 0.5 µM, and 1.0 µM), on the proliferation, apoptosis, and progenitor integrity of these cells. To do this, HPCs were exposed to these concentrations for 48 h, followed by immunocytochemistry to quantify, cell number (DAPI-positive cells), proliferation (KI67-positve cells), apoptosis (CC3-positve cells), and progenitor integrity (SOX2- and Nestin-positive cells). While our results indicated no significant effects of selenium concentrations on proliferation or apoptosis, we demonstrated that absence of selenium (0 μM) in the culture media significantly reduced both cell number and percentage of Nestin-positive cells, but only when compared to the condition with the highest selenium concentration (1.0 μM). Our findings underscore the role of selenium in regulating the survival and integrity of human HPCs. Lastly, we emphasize the need for further research to uncover the mechanisms underlying these observed changes.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"7 ","pages":"Article 100138"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891489","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}

引用次数: 0

Effects of global Ripk2 genetic deficiency in aged mice following experimental ischemic stroke Ripk2基因缺失对实验性缺血性脑卒中老年小鼠的影响

IF 1.7

Aging brain Pub Date : 2025-01-01 DOI: 10.1016/j.nbas.2025.100135

John Aaron Howell , Jonathan Larochelle , Rachel E. Gunraj , Sofia M. Stansbury , Lei Liu , Changjun Yang , Eduardo Candelario-Jalil

{"title":"Effects of global Ripk2 genetic deficiency in aged mice following experimental ischemic stroke","authors":"John Aaron Howell , Jonathan Larochelle , Rachel E. Gunraj , Sofia M. Stansbury , Lei Liu , Changjun Yang , Eduardo Candelario-Jalil","doi":"10.1016/j.nbas.2025.100135","DOIUrl":"10.1016/j.nbas.2025.100135","url":null,"abstract":"<div><div>Besides the loss of blood and oxygen reaching the ischemic tissue, many secondary effects of ischemic stroke can cause additional tissue damage, including inflammation, oxidative stress, and proteomic disturbances. Receptor-interacting serine/threonine kinase 2 (RIPK2) is an important mediator in the post-stroke inflammatory cascade that responds to signals and molecular patterns released by dead or dying cells in the ischemic area. We hypothesize that RIPK2 signaling worsens injury and neurological recovery post-stroke and that global deletion of <em>Ripk2</em> is protective following ischemic stroke in aged mice. Aged (18–24 months) male mice were subjected to permanent middle cerebral artery occlusion (pMCAO). Vertical grid, weight grip, and open field were conducted at baseline and on days 1, 2, 3, 8, 15, and 22 post-stroke. Cognitive tests (novel object recognition and Y-maze) were performed at baseline and day 28 post-stroke. Infarct size was measured using cresyl violet staining, and reactive gliosis was measured using Iba1 and GFAP staining at day 28 post-stroke. Global deletion of <em>Ripk2</em> (<em>Ripk2<sup>-/-</sup></em>) in aged mice resulted in smaller infarct volume and improved performance on vertical grid and weight grip tests compared to aged wildtype (WT) mice. Additionally, aged <em>Ripk2</em><sup>-/-</sup> mice had less Iba1 staining in the ipsilateral cortex than the aged WT control mice. This study further elucidates the role of RIPK2 signaling in the ischemic cascade and expands our knowledge of RIPK2 in stroke to aged mice. These results support the hypothesis that RIPK2 signaling worsens injury post-stroke and may be an attractive candidate for therapeutic intervention.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"7 ","pages":"Article 100135"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

White matter differences between younger and older adults revealed by fixel-based analysis 基于固定颗粒的分析揭示了年轻人和老年人的白质差异

IF 1.7

Aging brain Pub Date : 2024-01-01 DOI: 10.1016/j.nbas.2024.100132

Feliberto de la Cruz , Andy Schumann , Katrin Rieger , Daniel Güllmar , Jürgen R. Reichenbach , Karl-Jürgen Bär

{"title":"White matter differences between younger and older adults revealed by fixel-based analysis","authors":"Feliberto de la Cruz , Andy Schumann , Katrin Rieger , Daniel Güllmar , Jürgen R. Reichenbach , Karl-Jürgen Bär","doi":"10.1016/j.nbas.2024.100132","DOIUrl":"10.1016/j.nbas.2024.100132","url":null,"abstract":"<div><div>The process of healthy aging involves complex alterations in neural structures, with white matter (WM) changes significantly impacting cognitive and motor functions. Conventional methods such as diffusion tensor imaging provide valuable insights, but their limitations in capturing complex WM geometry advocate for more advanced approaches. In this study involving 120 healthy volunteers, we investigated whole-brain WM differences between young and old individuals using a novel technique called fixel-based analysis (FBA). This approach revealed that older adults exhibited reduced FBA-derived metrics in several WM tracts, with frontal areas particularly affected. Surprisingly, age-related differences in FBA-derived measures showed no significant correlation with risk factors such as alcohol consumption, exercise frequency, or pulse pressure but predicted cognitive performance. These findings emphasize FBA’s potential in characterizing complex WM changes and the link between cognitive abilities and WM alterations in healthy aging. Overall, this study advances our understanding of age-related neurodegeneration, highlighting the importance of comprehensive assessments that integrate advanced neuroimaging techniques, cognitive evaluation, and demographic factors to gain insights into healthy aging.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"6 ","pages":"Article 100132"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Longitudinal data are crucial for identifying superagers 纵向数据对确定超级用户至关重要

Aging brain Pub Date : 2024-01-01 DOI: 10.1016/j.nbas.2024.100118

Lars Nyberg

引用次数: 0

Targeted brain-specific tauopathy compromises peripheral skeletal muscle integrity and function 脑特异性牛磺酸病损害外周骨骼肌的完整性和功能

Aging brain Pub Date : 2024-01-01 DOI: 10.1016/j.nbas.2024.100110

Bryan Alava , Gabriela Hery , Silvana Sidhom , Miguel Gutierrez-Monreal , Stefan Prokop , Karyn A. Esser , Jose Abisambra

{"title":"Targeted brain-specific tauopathy compromises peripheral skeletal muscle integrity and function","authors":"Bryan Alava , Gabriela Hery , Silvana Sidhom , Miguel Gutierrez-Monreal , Stefan Prokop , Karyn A. Esser , Jose Abisambra","doi":"10.1016/j.nbas.2024.100110","DOIUrl":"https://doi.org/10.1016/j.nbas.2024.100110","url":null,"abstract":"<div><p>Tauopathies are neurodegenerative disorders in which the pathological intracellular aggregation of the protein tau causes cognitive deficits. Additionally, clinical studies report muscle weakness in populations with tauopathy. However, whether neuronal pathological tau species confer muscle weakness, and whether skeletal muscle maintains contractile capacity in primary tauopathy remains unknown. Here, we identified skeletal muscle abnormalities in a mouse model of primary tauopathy, expressing human mutant P301L-tau using adeno-associated virus serotype 8 (AAV8). AAV8-P301L mice showed grip strength deficits, hyperactivity, and abnormal histological features of skeletal muscle. Additionally, spatially resolved gene expression of muscle cross sections were altered in AAV8-P301L myofibers. Transcriptional changes showed alterations of genes encoding sarcomeric proteins, proposing a weakness phenotype. Strikingly, specific force of the soleus muscle was blunted in AAV8-P301L tau male mice. Our findings suggest tauopathy has peripheral consequences in skeletal muscle that contribute to weakness in tauopathy.</p></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"5 ","pages":"Article 100110"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589958924000057/pdfft?md5=9013d5b5fc8f1c0ab274640c4767554a&pid=1-s2.0-S2589958924000057-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cognitive and gray matter volume predictors of learning across two types of casual video games in older Adults: Action vs Strategy 预测老年人学习两种类型休闲电子游戏的认知和灰质体积：动作与策略

IF 1.7

Aging brain Pub Date : 2024-01-01 DOI: 10.1016/j.nbas.2024.100131

Evan T. Smith , Kaoru Nashiro , Margaret O’Connell , Xi Chen , Chandramallika Basak

{"title":"Cognitive and gray matter volume predictors of learning across two types of casual video games in older Adults: Action vs Strategy","authors":"Evan T. Smith , Kaoru Nashiro , Margaret O’Connell , Xi Chen , Chandramallika Basak","doi":"10.1016/j.nbas.2024.100131","DOIUrl":"10.1016/j.nbas.2024.100131","url":null,"abstract":"<div><div>Video game based and other computerized cognitive interventions are generally efficacious in bolstering cognition in adults over the age of 60, though specific efficacy varies widely by intervention methodology. Furthermore, there is reason to suspect that the process of learning complex tasks like video games is a major factor underpinning training-related transfer to cognition. The current study examined the neurocognitive predictors of learning of video games, and how those predictors may differentially relate to games of different genres. Learning rates from two different types of games, one action and another strategy, were calculated for 32 older adults (mean age = 66.29 years, 65 % Female). An extensive cognitive battery as well as structural measures of regional gray matter volumes were examined to identify the cognitive and the brain structure contributors to the learning rates for each type of game. A broad leftlateralized gray matter volume construct, as well as cognitive constructs of processing speed, episodic memory and reasoning, were found to significantly predict learning of the Strategy game, but not the Action game. Additionally, this gray matter construct was found to entirely mediate the relationships between the Strategy game learning and cognition, esp. episodic memory and reasoning. The contributions of age-sensitive cognitive skills as well as related brain volumes of lateral fronto-parietal regions to Strategy video games implicate the examined game as a potential game training tool in normal aging.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"6 ","pages":"Article 100131"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0