Neurobiology of Aging最新文献

{"title":"Mnemonic brain state engagement is diminished in healthy aging","authors":"Isabelle L. Moore,&nbsp;Devyn E. Smith,&nbsp;Nicole M. Long","doi":"10.1016/j.neurobiolaging.2025.03.012","DOIUrl":"10.1016/j.neurobiolaging.2025.03.012","url":null,"abstract":"<div><div>Healthy older adults typically show impaired episodic memory – memory for when and where an event occurred. This selective episodic memory deficit may arise from differential engagement in the retrieval state, a brain state in which attention is focused internally in an attempt to access prior knowledge, and the encoding state, a brain state which supports the formation of new memories and that trades off with the retrieval state. We hypothesize that older adults are biased toward a retrieval state. We recorded scalp electroencephalography while young, middle-aged and older adults performed a memory task in which they were explicitly directed to either encode or retrieve on a given trial. We used multivariate pattern analysis of spectral activity to decode retrieval vs. encoding state engagement. We find that whereas all age groups can follow task demands to selectively engage in encoding or retrieval, mnemonic brain state engagement is diminished for older adults relative to young and middle-aged adults. These findings suggest that differential mnemonic state engagement may underlie age-related memory changes.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"151 ","pages":"Pages 76-88"},"PeriodicalIF":3.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835015","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}

{"title":"Dynamics and role of covalently-closed circular RNAs in Alzheimer's disease: A review of experimental and bioinformatics studies","authors":"Nikta Zafarjafarzadeh ,&nbsp;Elham Feridouni ,&nbsp;Sudabe Sobhani-Moghaddam ,&nbsp;Javad Amini ,&nbsp;Samaneh Mollazadeh ,&nbsp;Reza Ataei ,&nbsp;Hamed Ghomi ,&nbsp;Cordian Beyer ,&nbsp;Nima Sanadgol","doi":"10.1016/j.neurobiolaging.2025.04.002","DOIUrl":"10.1016/j.neurobiolaging.2025.04.002","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is an age-associated disorder characterized by cognitive decline, with dementia representing the final stage of a complex clinical-biological process rather than simply a more severe form of cognitive decline. Circular RNAs (circRNAs), novel non-coding RNAs, have emerged as key regulators of brain function and associated disorders. This study explores the role of circRNAs in AD by reviewing experimentally validated circRNAs in human and animal models. We identified 10 human (seven pathogenic, three protective) and six animal (three pathogenic, three protective) AD-related circRNAs. Experimental studies have confirmed that human protective circRNAs are predominantly downregulated in AD, where they function by sequestering specific miRNAs within cells, particularly miR-7, miR-142–5p, and miR-217, which have well-recognized neuroinflammatory functions. In-silico analysis revealed that circLPAR1 (pathogenic), circHUWE1 (pathogenic), and circHOMER1 (protective) interact with miRNAs that mainly control AD-related genes. Notably, circHOMER1 plays a key role in regulating multiple AD-related pathways, including autophagy, apoptosis, and PI3K-AKT and amyloid fiber formation. Furthermore, circRNA/protein interaction analysis revealed that circHUWE1 predominantly associates with RNA transport proteins, whereas circHOMER1 interacts with proteins involved in mRNA surveillance pathways. Remarkably, docking analysis demonstrated that circAβ-a (pathogenic) exhibits a strong affinity for eukaryotic translation initiation factor 4A3 protein, while circHOMER1 shows a higher binding affinity for DGCR8 microprocessor complex subunit protein. Our study presents a concise list of circRNAs as potential key targets for further investigation in AD research. Future experimental research is essential to uncover their precise mechanisms and assess their potential as biomarkers, offering promising avenues for developing interventions to alleviate cognitive decline in AD.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"151 ","pages":"Pages 54-69"},"PeriodicalIF":3.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829186","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}

{"title":"Higher soluble ADAM10 plasma levels are associated with decreased cognitive performance in older adults carrying APOEε4","authors":"Lucas Nogueira de Carvalho Pelegrini ,&nbsp;Patricia Regina Manzine ,&nbsp;Cecilia Patricia Popolin ,&nbsp;Sabrina Dorta ,&nbsp;Marina Mantellatto Grigoli ,&nbsp;Vanessa Alexandre-Silva ,&nbsp;Renata Pedroso ,&nbsp;Ari Alex Ramos ,&nbsp;Henrique Pott ,&nbsp;Marcia Regina Cominetti","doi":"10.1016/j.neurobiolaging.2025.04.003","DOIUrl":"10.1016/j.neurobiolaging.2025.04.003","url":null,"abstract":"<div><div>The APOE gene, particularly its ε4 allele, is a significant genetic risk factor for Alzheimer’s disease (AD) and influences amyloid-β (Aβ) pathology and cognitive decline. This study explores the relationship between APOEε4 genotype, plasma levels of soluble ADAM10 (sADAM10), and cognitive performance in cognitively unimpaired (CU) older adults and those with AD dementia. It is a cross-sectional analysis that included 85 participants assessed for cognitive function, APOE genotype, and plasma sADAM10 levels. ADAM10, a key enzyme in the non-amyloidogenic pathway of Aβ precursor protein (APP) processing, has emerged as a promising biomarker due to its altered levels in AD patients. Our findings revealed significantly higher plasma sADAM10 levels in AD participants compared to CU individuals, with APOEε4 carriers exhibiting a nearly twofold increase in sADAM10 levels. A negative correlation was observed between plasma sADAM10 concentrations and cognitive performance, independent of APOEε4 status. Notably, the study highlights the potential of sADAM10 as a blood-based biomarker, emphasizing its relevance in APOEε4-mediated AD pathology. Importantly, most studies exploring ADAM10 and APOE interactions have been conducted in high-income countries, limiting the generalizability of their findings to diverse populations. This study is the first to be conducted in a Global South country, offering critical insights into underrepresented populations and underscoring the need for more inclusive research in AD. Future research should include larger cohorts and longitudinal designs to validate these findings and explore targeted interventions leveraging sADAM10 activity in the context of APOEε4-associated AD progression.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"151 ","pages":"Pages 70-75"},"PeriodicalIF":3.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835014","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}

{"title":"Editorial Advisory Board","authors":"","doi":"10.1016/S0197-4580(25)00064-8","DOIUrl":"10.1016/S0197-4580(25)00064-8","url":null,"abstract":"","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"150 ","pages":"Page IFC"},"PeriodicalIF":3.7,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lower aperiodic EEG activity is associated with reduced verbal fluency performance across adulthood","authors":"Daniel J. McKeown ,&nbsp;Emily Roberts ,&nbsp;Anna J. Finley ,&nbsp;Nicholas J. Kelley ,&nbsp;Hannah A.D. Keage ,&nbsp;Victor R. Schinazi ,&nbsp;Oliver Baumann ,&nbsp;Ahmed A. Moustafa ,&nbsp;Douglas J. Angus","doi":"10.1016/j.neurobiolaging.2025.03.013","DOIUrl":"10.1016/j.neurobiolaging.2025.03.013","url":null,"abstract":"<div><div>Age-related cognitive decline associations with human electroencephalography (EEG) have previously focused on periodic activity. However, EEG primarily consists of non-oscillatory aperiodic activity, characterised with an exponent and offset value. In a secondary analysis of a cohort of 111 healthy participants aged 17 – 71 years, we examined the associations of the aperiodic exponent and offset in resting EEG with a battery of cognitive tests consisting of the Colour-Word Interference Test, Wechsler Adult Intelligence Scale IV Digit Span Test, Rey Auditory Learning Test, Delis-Kaplan Executive Function System Trail Making Test, and the Verbal Fluency Test. Using Principal Component Analysis and K-Means Clustering, we identified clusters of electrodes that exhibited similar aperiodic exponent and offset activity during resting-state eyes-closed EEG. Robust linear models were then used to model how aperiodic activity interacted with age and their associations with performance during each cognitive test. Offset by age interactions were identified for the Verbal Fluency Test, where smaller offsets were associated with poorer performance in adults as early as 33 years of age. Greater aperiodic activity is increasingly related to better verbal fluency performance with age in adulthood.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"151 ","pages":"Pages 29-41"},"PeriodicalIF":3.7,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143807426","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}

{"title":"Brain microRNAs differentially expressed in age-related cerebral pathologies","authors":"Tianze Luo ,&nbsp;Selina M. Vattathil ,&nbsp;Adriana Lori ,&nbsp;Julie A. Schneider ,&nbsp;David A. Bennett ,&nbsp;Thomas S. Wingo ,&nbsp;Aliza P. Wingo","doi":"10.1016/j.neurobiolaging.2025.03.014","DOIUrl":"10.1016/j.neurobiolaging.2025.03.014","url":null,"abstract":"<div><div>Multiple brain pathologies accumulate with age, but their underlying biology remains unclear. We investigated the role of microRNAs (miRNAs) in ten age-related cerebral pathologies. Using miRNA sequencing profiles from the dorsolateral prefrontal cortex of 617 brain donors, we identified miRNAs associated with Alzheimer’s disease (AD) pathology, Lewy body pathology, arteriolosclerosis, cerebral amyloid angiopathy, and LATE-NC after adjusting for age, sex, and education. After additionally adjusting for co-existing cerebral pathologies, we found miRNAs specifically associated with AD pathology (n = 75), Lewy body pathology (n = 45), arteriolosclerosis (n = 3), cerebral amyloid angiopathy (n = 1), and LATE-NC (n = 4). While some miRNAs were pathology-specific, 14 miRNAs (including those in the miR-132/212 cluster) were associated with both AD pathology and Lewy body pathology, and one (miR-193a-5p) was associated with both AD pathology and cerebral amyloid angiopathy. Gene set enrichment analysis showed that miRNAs associated with arteriolosclerosis target genes involved in glutathione metabolism, synaptic functions, cellular transport, and innate immune response. These findings highlight the role of miRNAs in age-related cerebral pathologies and provide a foundation for future mechanistic studies.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"151 ","pages":"Pages 42-53"},"PeriodicalIF":3.7,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823954","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}

{"title":"Gene age gap estimate (GAGE) for major depressive disorder: A penalized biological age model using gene expression","authors":"Yijie (Jamie) Li ,&nbsp;Rayus Kuplicki ,&nbsp;Bart N. Ford ,&nbsp;Elizabeth Kresock ,&nbsp;Leandra Figueroa-Hall ,&nbsp;Jonathan Savitz ,&nbsp;Brett A. McKinney","doi":"10.1016/j.neurobiolaging.2025.01.012","DOIUrl":"10.1016/j.neurobiolaging.2025.01.012","url":null,"abstract":"<div><div>Recent associations between Major Depressive Disorder (MDD) and measures of premature aging suggest accelerated biological aging as a potential biomarker for MDD susceptibility or MDD as a risk factor for age-related diseases. Residuals or “gaps” between the predicted biological age and chronological age have been used for statistical inference, such as testing whether an increased age gap is associated with a given disease state. Recently, a gene expression-based model of biological age showed a higher age gap for individuals with MDD compared to healthy controls (HC). In the current study, we propose an approach that simplifies gene selection using a least absolute shrinkage and selection operator (LASSO) penalty to construct an expression-based Gene Age Gap Estimate (GAGE) model. We train a LASSO gene age model on an RNA-Seq study of 78 unmedicated individuals with MDD and 79 HC, resulting in a model with 21 genes. The L-GAGE shows higher biological aging in MDD participants than HC, but the elevation is not statistically significant. However, when we dichotomize chronological age, the interaction between MDD status and age has a significant association with L-GAGE. This effect remains statistically significant even after adjusting for chronological age and sex. Using the 21 age genes, we find a statistically significant elevated biological age in MDD in an independent microarray gene expression dataset. We find functional enrichment of infectious disease and SARS-COV pathways using a broader feature selection of age related genes.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"151 ","pages":"Pages 13-21"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767827","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}

{"title":"A more irregular shape of white matter hyperintensities is associated with cognitive decline over five years in community-dwelling older adults","authors":"Jasmin Annica Kuhn-Keller ,&nbsp;Sigurdur Sigurdsson ,&nbsp;Lenore J. Launer ,&nbsp;Mark A. van Buchem ,&nbsp;Matthias J.P. van Osch ,&nbsp;Vilmundur Gudnason ,&nbsp;Jeroen de Bresser","doi":"10.1016/j.neurobiolaging.2025.03.011","DOIUrl":"10.1016/j.neurobiolaging.2025.03.011","url":null,"abstract":"<div><div>WMH shape is associated with long-term risk for dementia after 10 years in community-dwelling older adults. The current study aimed to investigate the association of WMH shape and decline in three cognitive domains over five years’ time in community-dwelling older adults. The association of baseline WMH shape (solidity, convexity, concavity index, fractal dimension, and eccentricity) and cognitive decline over 5.2 ± 0.3 years (domains: memory, executive function, and processing speed) was investigated using linear regression models in the Age, Gene/Environment Susceptibility-Reykjavik (AGES) study (n = 2493). A more irregular shape of periventricular/confluent WMH was related to cognitive decline in the memory domain, the executive function domain, and the processing speed domain over five years (p &lt; 0.05). No associations were found between deep WMH shape and decline in the cognitive domains. These findings show that WMH shape patterns may be indicative of relatively short-term cognitive decline in community-dwelling older adults. This supports the evidence of WMH shape being a valuable marker that may be used to assess and predict cognitive outcome related to cerebrovascular disease progression.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"151 ","pages":"Pages 22-28"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific decline in prefrontal cortex mitochondrial bioenergetics in aging baboons correlates with walking speed","authors":"Daniel A. Adekunbi ,&nbsp;Hillary F. Huber ,&nbsp;Gloria A. Benavides ,&nbsp;Ran Tian ,&nbsp;Cun Li ,&nbsp;Peter W. Nathanielsz ,&nbsp;Jianhua Zhang ,&nbsp;Victor Darley-Usmar ,&nbsp;Laura A. Cox ,&nbsp;Adam B. Salmon","doi":"10.1016/j.neurobiolaging.2025.03.010","DOIUrl":"10.1016/j.neurobiolaging.2025.03.010","url":null,"abstract":"<div><div>Mitochondria play a crucial role in brain homeostasis and changes in mitochondrial bioenergetics are linked to age-related neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. We investigated changes in the activities of the electron transport chain (ETC) complexes in normally aging baboon brains and determined how these changes relate to donor sex, morning cortisol levels, and walking speed. We assessed mitochondrial bioenergetics from archived prefrontal cortex (PFC) tissues from a large cohort (60 individuals) of well-characterized aging baboons (6.6–22.8 years, approximately equivalent to 26.4–91.2 human years). Aging was associated with a decline in mitochondrial ETC complexes in the PFC, which was more pronounced when normalized for citrate synthase activity, suggesting that the decline is predominantly driven by changes in the specific activity of individual complexes rather than global changes in mitochondrial content. When donor sex was used as a covariate, we found that ETC activity was preserved with age in females and declined in males. Males had higher activities of each individual ETC complex and greater lactate dehydrogenase activity at a given age relative to females. Circulating cortisol negatively correlated with walking speed when male and female data were combined. We also observed a robust positive predictive relationship between walking speed and respiration linked to complexes I, III, and IV in males but not in females. This data reveals a link between frailty and PFC bioenergetic function and highlights a potential molecular mechanism for sexual dimorphism in brain resilience.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"151 ","pages":"Pages 1-12"},"PeriodicalIF":3.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724866","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}

{"title":"Long-term nucleus basalis cholinergic lesions alter the structure of cortical vasculature, astrocytic density and microglial activity in Wistar rats","authors":"Chiara Orciani ,&nbsp;Morgan K. Foret ,&nbsp;A. Claudio Cuello ,&nbsp;Sonia Do Carmo","doi":"10.1016/j.neurobiolaging.2025.03.006","DOIUrl":"10.1016/j.neurobiolaging.2025.03.006","url":null,"abstract":"<div><div>Basal forebrain cholinergic neurons (BFCNs) are the sole source of cholinergic innervation to the cerebral cortex and hippocampus in humans and the primary source in rodents. This system undergoes early degeneration in Alzheimer's disease. BFCNs terminal synapses are involved in the regulation of the cerebral blood flow by making classical synaptic contacts with other neurons. Additionally, they are located in proximity to cortical cerebral blood vessels, forming connections with various cell types of the neurovascular unit (NVU), including vascular smooth muscle cells, endothelial cells, and astrocytic end-feet. However, the effects of the BFCNs input on NVU components remain unresolved. To address this issue, we immunolesioned the nucleus basalis by administering bilateral stereotaxic injections of the cholinergic immunotoxin 192-IgG-Saporin in 2.5-month-old Wistar rats. Seven months post-lesion, we observed a significant reduction in cortical vesicular acetylcholine transporter-immunoreactive synapses. This was accompanied by changes in the diameter of cortical capillaries and precapillary arterioles, as well as lower levels of vascular endothelial growth factor A (VEGF-A). Additionally, the cholinergic immunolesion increased the density of cortical astrocytes and microglia in the cortex. At these post-BFCN-lesion stages, astrocytic end-feet exhibited an increased co-localization with arterioles. The number of microglia in the parietal cortex correlated with cholinergic loss and exhibited morphological changes indicative of an intermediate activation state. This was supported by decreased levels of proinflammatory mediators IFN-γ, IL-1β, and KC/GRO (CXCL1), and by increased expression of M2 markers SOCS3, IL4Rα, YM1, ARG1, and Fizz1. Our findings offer a novel insight: that the loss of nucleus basalis cholinergic input negatively impacts cortical blood vessels, NVU components, and microglia phenotype.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"150 ","pages":"Pages 132-145"},"PeriodicalIF":3.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}