Neurobiology of Aging最新文献_第5页

IF 3.5 3区医学

Neurobiology of Aging Pub Date : 2026-01-01 Epub Date: 2025-11-03 DOI: 10.1016/j.neurobiolaging.2025.10.007

Emily M. Fabrizio-Stover , James W. Dias , Carolyn M. McClaskey , Kelly C. Harris

{"title":"Age-related auditory nerve deficits propagate central gain throughout the auditory system: Associations with cortical microstructure and speech recognition","authors":"Emily M. Fabrizio-Stover , James W. Dias , Carolyn M. McClaskey , Kelly C. Harris","doi":"10.1016/j.neurobiolaging.2025.10.007","DOIUrl":"10.1016/j.neurobiolaging.2025.10.007","url":null,"abstract":"<div><div>There is growing evidence that perceptual difficulties associated with age-related hearing loss are not solely due to cochlear damage and are exacerbated by central nervous system changes. We examined electrophysiological (EEG) responses to clicks and diffusion kurtosis imaging in 49 older (29 female) and 26 younger (20 female) adults to determine the extent to which auditory nerve (AN) deficits in older adults contributed to functional and structural changes throughout the auditory system. Older adults exhibited smaller AN responses, similar brainstem responses, and larger auditory cortex (AC) responses, demonstrating progressive “central gain.” Audiometric thresholds were not predictive of EEG measures. Reduced AN function predicted deficits in cortical microstructure (lower AC fractional anisotropy) in older adults, consistent with microstructure degeneration. These lower fractional anisotropy values in the AC of older adults also predicted larger AC responses and more central gain. Older adults exhibited significantly lower AC fractional anisotropy and kurtosis fractional anisotropy coupled with higher mean and radial diffusivity compared to younger adults. AC fractional anisotropy, radial diffusivity, axial diffusivity, and mean diffusivity were all significant predictors of speech-in-noise (SIN) recognition in older adults. The results suggest that reduced afferent input in older adults not only results in functional changes throughout the auditory system consistent with progressive gain but also contributes to deficits in AC structure beyond those explained by age alone, contributing to SIN recognition deficits. Understanding the complex effects of age, reduced AN input, central gain, and AC microstructure on SIN recognition may provide potential therapeutic targets for intervention.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"157 ","pages":"Pages 98-110"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145459128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identifying a proteomics signature of cognitive impairment and dementia in blood and cerebrospinal fluid through a mediation analysis framework 通过中介分析框架确定血液和脑脊液中认知障碍和痴呆的蛋白质组学特征

IF 3.5 3区医学

Neurobiology of Aging Pub Date : 2026-01-01 Epub Date: 2025-10-28 DOI: 10.1016/j.neurobiolaging.2025.10.004

Gabriel Torrealba-Acosta , Shu Yang , Javier Calvo-Marín , Abhay R. Moghekar , Aida Kamalian , Michael W. Lutz , for the Alzheimer’s Disease Neuroimaging Initiative

{"title":"Identifying a proteomics signature of cognitive impairment and dementia in blood and cerebrospinal fluid through a mediation analysis framework","authors":"Gabriel Torrealba-Acosta , Shu Yang , Javier Calvo-Marín , Abhay R. Moghekar , Aida Kamalian , Michael W. Lutz , for the Alzheimer’s Disease Neuroimaging Initiative","doi":"10.1016/j.neurobiolaging.2025.10.004","DOIUrl":"10.1016/j.neurobiolaging.2025.10.004","url":null,"abstract":"<div><div>This study aimed to identify CSF and plasma proteins that mediate the association between age and mild cognitive impairment (MCI) and Alzheimer’s disease using mediation analysis. By focusing on proteins significantly associated in both CSF and plasma, we sought to identify biomarkers accessible for clinical applications. Proteomic measurements were obtained from CSF and plasma from a cohort of cognitively normal and MCI patients at the Johns Hopkins Alzheimer’s Disease Research Center using Olink Proximity Extension Assay technology. Mediation effects were estimated using single- and multiple-mediator models and validated in three independent datasets: Duke (CSF), ADNI (CSF), and UK Biobank (plasma). Over 3000 proteins in 86 patients were analyzed. Three candidates, leiomodin-1 (LMOD1), glial fibrillary acidic protein (GFAP), and elastin (ELN), met the criteria for mediation in both CSF and plasma. Multiple mediator models demonstrated a significant combined mediation effect on MCI in CSF (OR: 1.122, 95 % CI: 1.026–1.439) and plasma (OR: 1.142, 95 % CI: 1.058–1.410). Across validation cohorts, GFAP consistently showed significant mediation effects (Duke CSF: OR: 1.114, 95 % CI: 1.069–1.206; ADNI: OR: 1.004, 95 % CI: 1.000–1.009; UK Biobank: OR: 1.030, 95 % CI: 1.026–1.034). In contrast, ELN and LMOD1 demonstrated mediation effects in the discovery dataset but were not consistently reproduced in external cohorts. Our findings highlight GFAP as a robust mediator of age-related risk of cognitive impairment across CSF and plasma, supporting its utility as a practical biomarker. ELN and LMOD1 may represent exploratory candidates reflecting extracellular matrix and vascular processes requiring further validation.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"157 ","pages":"Pages 79-88"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145418220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Relationship between inner hair cell synaptopathy and outer hair cell loss in two mouse models of accelerated age-related hearing loss 两种老年性加速听力损失小鼠模型中内毛细胞突触病变与外毛细胞损失的关系

IF 3.5 3区医学

Neurobiology of Aging Pub Date : 2025-12-01 Epub Date: 2025-08-26 DOI: 10.1016/j.neurobiolaging.2025.08.006

Tuuli Lankinen, Saija Leinonen, Kuu Ikäheimo , Ulla Pirvola

{"title":"Relationship between inner hair cell synaptopathy and outer hair cell loss in two mouse models of accelerated age-related hearing loss","authors":"Tuuli Lankinen, Saija Leinonen, Kuu Ikäheimo , Ulla Pirvola","doi":"10.1016/j.neurobiolaging.2025.08.006","DOIUrl":"10.1016/j.neurobiolaging.2025.08.006","url":null,"abstract":"<div><div>Hallmarks of sensorineural hearing loss are elevated hearing thresholds and defects in temporal auditory processing, the former being often caused by outer hair cell (OHC) damage, and the latter by the loss of synapses between inner hair cells (IHCs) and spiral ganglion neurons. In the well-studied CBA/CaJ mouse strain, these impairments are disconnected, IHC synaptopathy preceding OHC loss. We have investigated the relationship between IHC synaptopathy and OHC loss in the C57BL/6J (B6) and ICR mouse strains that model accelerated age-related hearing loss. Regression analysis revealed a strong correlation between these variables across the high-to-low frequency axis of the cochlea. Using the fluorescent dye FM1–43 as a proxy for mechanotransduction (MET) in the hair-cell stereocilia bundle, we found that MET malfunction coexisted with synaptopathy in IHCs. Thus, our results suggest that a MET defect drives IHC synaptopathy in the B6 and ICR strains known to carry a missense mutation of <em>Cadherin 23,</em> encoding a stereocilia bundle protein. Previous data have suggested that OHC stereocilia abnormalities could trigger OHC death. Therefore, stereocilia defect could be a trigger of intracellular stress that drives both IHC synaptopathy and OHC loss. To determine whether tauroursodeoxycholic acid (TUDCA), known to target several stress signalling pathways, could influence cochlear pathology, we conducted long-term TUDCA delivery to ICR mice. TUDCA provided partial protection against IHC synaptopathy but did not prevent OHC loss. These results in two mouse models of accelerated cochlear pathology provide novel insights into the mechanisms behind age-related hearing loss.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"156 ","pages":"Pages 85-100"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Choroid plexus volume and its association with cognitive performance across the lifespan: Links to sleep quality and healthy brain aging 脉络膜丛体积及其与一生中认知表现的关系：与睡眠质量和健康的大脑老化有关

IF 3.5 3区医学

Neurobiology of Aging Pub Date : 2025-12-01 Epub Date: 2025-08-13 DOI: 10.1016/j.neurobiolaging.2025.08.003

Julia L. Becker , M. Ethan MacDonald , Kirstan A. Vessey , Rebecca J. Williams

{"title":"Choroid plexus volume and its association with cognitive performance across the lifespan: Links to sleep quality and healthy brain aging","authors":"Julia L. Becker , M. Ethan MacDonald , Kirstan A. Vessey , Rebecca J. Williams","doi":"10.1016/j.neurobiolaging.2025.08.003","DOIUrl":"10.1016/j.neurobiolaging.2025.08.003","url":null,"abstract":"<div><div>The choroid plexus (ChP) is implicated in inflammation and supports the clearance of waste byproducts, particularly those related to the pathogenesis of Alzheimer’s disease. Increases in ChP volume have been associated with older age and cognitive decline in both clinical and healthy cohorts. However, the clearance of waste products in the brain is also related to sleep, and sleep quality may contribute to ChP dysfunction and cognitive decline. In the present work, it was therefore hypothesized that the association between age and cognitive performance is mediated by ChP volume, however this is conditional on sleep quality. A moderated-mediation model was tested on a sample (<em>N</em> = 590) of healthy adults aged 18–87 years from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN). Results showed that the relationship between increasing age and decreased cognitive performance was partially mediated by ChP volume, however, this was not conditional on sleep quality. A moderation analysis indicated that the relationship between ChP volume and cognitive performance was moderated by age, with ChP enlargement associated with worse cognitive performance in participants older than 62 years. In participants younger than 62 years, sleep duration was associated with cognitive performance, but ChP volume was not. These findings provide support for the sensitivity of ChP volume to cognitive performance in older adults.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"156 ","pages":"Pages 40-49"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to “The moderating effect of cognitive reserve on the association between neuroimaging biomarkers and cognition: A systematic review” [Neurobiology of Aging, Volume 156, December 2025, Pages 10–29] “认知储备对神经成像生物标志物和认知之间关联的调节作用：系统综述”的更正[衰老神经生物学，156卷，2025年12月，第10-29页]。

IF 3.5 3区医学

Neurobiology of Aging Pub Date : 2025-12-01 Epub Date: 2025-09-10 DOI: 10.1016/j.neurobiolaging.2025.08.007

Lizhi Guo , Yajing Zhou , Hanna Lu , Helene H. Fung

引用次数: 0

The relationship between category-level neural differentiation and exploratory eye movements in healthy young and older adults 健康青年和老年人类别水平神经分化与探索性眼动的关系

IF 3.5 3区医学

Neurobiology of Aging Pub Date : 2025-12-01 Epub Date: 2025-09-16 DOI: 10.1016/j.neurobiolaging.2025.09.003

Sabina Srokova , Nehal S. Shahanawaz , Michael D. Rugg

{"title":"The relationship between category-level neural differentiation and exploratory eye movements in healthy young and older adults","authors":"Sabina Srokova , Nehal S. Shahanawaz , Michael D. Rugg","doi":"10.1016/j.neurobiolaging.2025.09.003","DOIUrl":"10.1016/j.neurobiolaging.2025.09.003","url":null,"abstract":"<div><div>Age-related neural dedifferentiation, characterized by lower selectivity of neural responses in high-level sensory cortex, is thought to be a major contributor to age-related cognitive decline. However, the mechanisms that underlie dedifferentiation are poorly understood. Building on prior evidence that exploratory eye movements differ with age, we investigated the role that eye movement might play in age-related declines in neural selectivity. Healthy young and older adults underwent fMRI with simultaneous eye-tracking as they viewed words paired with images of scenes and objects prior to a memory test. Consistent with numerous prior reports, multivoxel pattern similarity analysis (PSA) of the fMRI data revealed age-related neural dedifferentiation in scene-selective, but not object-selective cortex. Eye movements, operationalized as the number of gaze fixations made during stimulus viewing, were elevated in older adults. Analyses examining the relationship between trial-wise estimates of neural selectivity and fixation count revealed an age-invariant positive relationship in the object-selective lateral occipital complex. However, this association was age-dependent in scene-selective cortex, such that there was a robust positive relationship between scene selectivity and fixation count in young adults, but absent or attenuated effects were present in older adults. Lastly, scene-related selectivity in the parahippocampal place area predicted subsequent memory performance independently of age group and fixation counts at encoding. These findings suggest that age-related neural dedifferentiation in scene-selective cortex could be related to declines in the functional specificity of exploratory eye movements during scene viewing.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"156 ","pages":"Pages 163-177"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Degeneration of the stria vascularis in quiet-aged gerbils: Linking structural, cellular and molecular changes to cochlear function 静龄沙鼠血管纹退化：结构、细胞和分子变化与耳蜗功能的联系

IF 3.5 3区医学

Neurobiology of Aging Pub Date : 2025-12-01 Epub Date: 2025-08-14 DOI: 10.1016/j.neurobiolaging.2025.08.004

Sonny Bovee , Carolin Jüchter , Georg M. Klump , Christine Köppl , Sonja J. Pyott

{"title":"Degeneration of the stria vascularis in quiet-aged gerbils: Linking structural, cellular and molecular changes to cochlear function","authors":"Sonny Bovee , Carolin Jüchter , Georg M. Klump , Christine Köppl , Sonja J. Pyott","doi":"10.1016/j.neurobiolaging.2025.08.004","DOIUrl":"10.1016/j.neurobiolaging.2025.08.004","url":null,"abstract":"<div><div>Presbycusis, or age-related hearing loss, is a prevalent condition characterized by progressive auditory decline, significantly impacting quality of life in older adults. While sensorineural damage has been widely studied, degeneration of the stria vascularis (SV) remains underexplored despite its essential role in cochlear ion homeostasis. The SV is organized into three cellular layers—marginal, intermediate, and basal cells—each with distinct functions critical for maintaining the endocochlear potential. Using the quiet-aged Mongolian gerbil—a well-established model of metabolic presbycusis—we systematically mapped the structural and cellular degeneration of the SV and linked these changes to cochlear function. We assessed cochlear function using auditory brainstem response (ABR) measurements and quantified age-related atrophy of the strial cell layers using immunofluorescence, confocal microscopy, and 3D reconstruction. We identified a striking, region-specific pattern of degeneration, with the greatest atrophy occurring in ATP1A1-expressing marginal cells, followed by KCNJ10-expressing intermediate cells, and comparatively little atrophy in CLDN11-expressing basal cells. Notably, atrophy was most pronounced in the cochlear apex and base, regions critical for low- and high-frequency hearing. We further established a significant correlation between the decline in cochlear function and the extent of atrophy of the individual strial cell layers, especially in the cochlear base. By moving beyond traditional cross-sectional assessments of age-related degeneration of the SV, this work provides a more nuanced understanding of how strial pathology contributes to age-related decline in cochlear function and may inform therapeutic interventions targeting strial function to mitigate age-related hearing loss even when sensorineural function is compromised.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"156 ","pages":"Pages 50-62"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Editorial Advisory Board 编辑顾问委员会

IF 3.5 3区医学

Neurobiology of Aging Pub Date : 2025-12-01 Epub Date: 2025-10-16 DOI: 10.1016/S0197-4580(25)00176-9

引用次数: 0

A synthetic nonapeptide, JAL-TA9, inhibits neuronal cytotoxicity caused by Aβ25–35 aggregation with proteolytic activity 合成的非肽JAL-TA9具有蛋白水解活性，可抑制Aβ25 - 35聚集引起的神经元细胞毒性

IF 3.5 3区医学

Neurobiology of Aging Pub Date : 2025-12-01 Epub Date: 2025-09-03 DOI: 10.1016/j.neurobiolaging.2025.09.001

Rina Nakamura , Momoka Okada , Asuka Takahashi , Yoshihiro Hayashi , Motomi Konishi , Fumiaki Ito , Ichiro Murakami , Motoaki Saito , Toshifumi Akizawa

{"title":"A synthetic nonapeptide, JAL-TA9, inhibits neuronal cytotoxicity caused by Aβ25–35 aggregation with proteolytic activity","authors":"Rina Nakamura , Momoka Okada , Asuka Takahashi , Yoshihiro Hayashi , Motomi Konishi , Fumiaki Ito , Ichiro Murakami , Motoaki Saito , Toshifumi Akizawa","doi":"10.1016/j.neurobiolaging.2025.09.001","DOIUrl":"10.1016/j.neurobiolaging.2025.09.001","url":null,"abstract":"<div><div>Due to the growing number of Alzheimer’s disease (AD) patients, new drugs are urgently required. A synthetic nonapeptide, JAL-TA9 (YKGSGFRMI), derived from Transducer of ErbB-2.1 (Tob1) protein, cleaves amyloid β (Aβ) 42 with serine protease-like activity. Aβ25–35 was chosen because it is the shortest fragment that forms fibrils and is cytotoxic. Aβ25–35 has been used to create AD model mice, and it appears to be an attractive target for AD therapeutics. Using Thioflavin-T assays, the fluorescence intensity of the reaction of Aβ25–35 and JAL-TA9 was lower than that of Aβ25–35 without JAL-TA9, and the same result was obtained with aggregated Aβ25–35. These data showed that JAL-TA9 inhibits aggregation of Aβ25–35 and dissolves its aggregates. Furthermore, electron microscopy showed that amyloid fibrils of both Aβ25–35 and aggregated Aβ25–35 are reduced in the presence of JAL-TA9. The proteolytic activity of JAL-TA9 against Aβ25–35 was evaluated using HPLC and mass spectrometry. These data showed that JAL-TA9 cleaves both soluble and aggregated forms of Aβ25–35. JAL-TA9 inhibits neuronal cytotoxicity caused by Aβ25–35 aggregation by cleaving Aβ25–35 and its aggregated form. These results suggest that JAL-TA9 is a promising candidate for developing novel drugs against AD.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"156 ","pages":"Pages 123-132"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to “Theta-gamma transcranial alternating current stimulation enhances ballistic motor performance in healthy young and older adults” [Neurobiol. Aging 152 (2025) 1–12] “Theta-gamma经颅交流电刺激增强健康年轻人和老年人的弹道运动表现”的勘误表[神经生物学]。老龄化[j]。

IF 3.5 3区医学

Neurobiology of Aging Pub Date : 2025-12-01 Epub Date: 2025-09-26 DOI: 10.1016/j.neurobiolaging.2025.09.005

N.N. Gamage , Wei-Yeh Liao , B.J. Hand , P.J. Atherton , M. Piasecki , G.M. Opie , J.G. Semmler

引用次数: 0