Neurobiology of Aging最新文献

{"title":"Effects of age and dietary methionine restriction on cognitive and behavioural phenotypes in the rTg4510 mouse model of frontotemporal dementia.","authors":"Marina Souza Matos, Annesha Sil, Gernot Riedel, Bettina Platt, Mirela Delibegovic","doi":"10.1016/j.neurobiolaging.2024.11.004","DOIUrl":"https://doi.org/10.1016/j.neurobiolaging.2024.11.004","url":null,"abstract":"<p><p>Metabolic disorders such as diabetes and obesity are linked to neurodegenerative diseases, with evidence of lower brain glucose metabolism and insulin resistance in dementia patients. Dietary methionine restriction (MR) is a nutritional intervention that enhances insulin sensitivity and delays ageing-associated metabolic alterations, however, its impact on neurodegenerative diseases is not fully understood. Here, we examined the behavioural and metabolic phenotypes of a murine tauopathy model (rTg4510), which overexpresses human P301L mutated tau, at 6 and 12 months of age, assessing the impact of an 8-week dietary MR in the older group. While rTg4510 mice displayed progressive behavioural and motor impairments at both ages, MR led to significant benefits in the 12-month-old cohort, improving motor coordination, short-term memory, and social recognition. These effects were accompanied by increased glycolysis markers and FGF21R1 levels in the hippocampus, alongside unaltered glucose metabolism/adiposity. Overall, our results reveal the impact of MR on an FTD-mouse model, suggesting this as a potential therapeutic intervention to delay and/or improve the progression of tau-related disease.</p>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"146 ","pages":"24-37"},"PeriodicalIF":3.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692930","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":"Cross-sectional and longitudinal relationships among blood-brain barrier disruption, Alzheimer's disease biomarkers, and cognition in cognitively normal older adults.","authors":"Marisa Denkinger, Suzanne Baker, Theresa M Harrison, Trevor Chadwick, William J Jagust","doi":"10.1016/j.neurobiolaging.2024.11.002","DOIUrl":"https://doi.org/10.1016/j.neurobiolaging.2024.11.002","url":null,"abstract":"<p><p>Blood-brain barrier disruption (BBBd) occurs in aging, particularly in regions vulnerable to Alzheimer's disease (AD) pathology. However, its relationship to pathological protein accumulation, neurodegeneration, and cognitive impairment in normal aging is unclear. We used dynamic contrast-enhanced MRI (DCE-MRI) and positron emission tomography (PET) imaging in cognitively normal older adults to explore how BBBd correlates with brain atrophy and cognitive function, and whether these relationships are influenced by Aβ or tau. We found that greater BBBd in the hippocampus (HC) and an averaged BBBd-susceptible ROI were linked to worse episodic memory, with interactions between BBBd and atrophy influencing this relationship, independent of Aβ and tau. However, there were no significant relationships between BBBd and non-memory cognitive performance. In participants with longitudinal AD biomarker and cognitive data acquired prior to DCE-MRI, faster longitudinal entorhinal cortex (EC) tau accumulation and episodic memory decline were associated with greater HC BBBd, independent of global Aβ changes and regional atrophy. These findings enhance our understanding of the complex relationships between AD biomarkers, cognitive decline, and BBBd.</p>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"146 ","pages":"15-23"},"PeriodicalIF":3.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687714","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":"Calcineurin/NFAT inhibitors maintain cognition in a preclinical prevention study in an aging canine model of Alzheimer disease","authors":"Lorena Sordo ,&nbsp;Margo F. Ubele ,&nbsp;Kathy A. Boaz ,&nbsp;Jennifer L. Mefford ,&nbsp;Erin Dehnart Jones ,&nbsp;Katie L. McCarty ,&nbsp;Hollie Y. van Rooyen ,&nbsp;Jeffrey Smiley ,&nbsp;Stasia A. Bembenek Bailey ,&nbsp;Jessica A. Perpich ,&nbsp;Beverly Meacham ,&nbsp;David K. Powell ,&nbsp;Frederick Bresch ,&nbsp;Jacob W. Crump ,&nbsp;Michael J. Phelan ,&nbsp;Jessica A. Noche ,&nbsp;Craig E. Stark ,&nbsp;László G. Puskás ,&nbsp;Christopher M. Norris ,&nbsp;Elizabeth Head","doi":"10.1016/j.neurobiolaging.2024.11.003","DOIUrl":"10.1016/j.neurobiolaging.2024.11.003","url":null,"abstract":"<div><div>Brain signaling of calcineurin (CN) and nuclear factor of activated T-cells (NFAT) transcription factor increases in Alzheimer disease (AD) and is associated with synaptic loss, neurodegeneration, neuroinflammation, amyloid-β (Aβ) production, and cognitive decline. CN/NFAT inhibitors ameliorate these neuropathologies in mouse models of AD. Further, chronic use of tacrolimus in transplant patients reduces risk of AD. Beagles naturally develop Aβ plaques and cognitive dysfunction. We evaluated the impact of FDA-approved CN inhibitor, tacrolimus, and experimental NFAT inhibitor, Q134R, on cognitive outcomes during a three-year prevention study in 37 middle-aged beagles. While beagles treated with CN/NFAT inhibitors showed differences in the pattern of cognitive maintenance and duration of their effect, there was improvement in spatial learning, as well as maintenance of memory, attention, and working memory relative to placebo dogs. CN/NFAT inhibition is a promising target for prevention of cognitive decline that may be rapidly implemented in human clinical trials.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"146 ","pages":"Pages 1-14"},"PeriodicalIF":3.7,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639053","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":"Hypertension may associate with cerebral small vessel disease and infarcts through the pathway of intracranial atherosclerosis","authors":"Marcelo Kenzo Naya Takahashi ,&nbsp;Regina Silva Paradela ,&nbsp;Lea Tenenholz Grinberg ,&nbsp;Renata Elaine Paraizo Leite ,&nbsp;Daniela Souza Farias-Itao ,&nbsp;Vitor Ribeiro Paes ,&nbsp;Maria Eduarda Braga ,&nbsp;Michel Satya Naslavsky ,&nbsp;Mayana Zatz ,&nbsp;Wilson Jacob-Filho ,&nbsp;Ricardo Nitrini ,&nbsp;Carlos Augusto Pasqualucci ,&nbsp;Claudia Kimie Suemoto","doi":"10.1016/j.neurobiolaging.2024.11.001","DOIUrl":"10.1016/j.neurobiolaging.2024.11.001","url":null,"abstract":"<div><div>Hypertension, a major modifiable risk factor for cardiovascular diseases, is linked to late-life neurocognitive disorders such as vascular dementia and Alzheimer's disease (AD). This study explores the associations between hypertension, intracranial atherosclerotic disease (ICAD), cerebral small vessel disease (cSVD), and Alzheimer's disease neuropathologic change (ADNC) in a large community-based autopsy study.</div><div>This cross-sectional study used data from the Biobank for Aging Studies of the University of São Paulo Medical School. Sociodemographic and clinical information was gathered from a reliable next-of-kin informant. Neurofibrillary tangles, neuritic plaques, lacunar infarcts, hyaline arteriolosclerosis, and cerebral amyloid angiopathy were evaluated. Causal mediation analyses with natural effect models were performed to examine indirect associations of hypertension with cerebrovascular pathologies and ADNC through morphometric measurements of intracranial artery lumen obstruction.</div><div>Hypertensive participants (n = 354) presented a higher rate of stenosed arteries (obstruction ≥ 50 %), critically stenosed arteries (obstruction ≥ 70 %), and more severe ICAD, shown by higher maximum and mean obstruction indexes compared to nonhypertensive participants (n = 166). These measurements of atherosclerosis were associated with neurofibrillary tangles and cSVD lesions. Hypertension was indirectly associated with hyaline arteriolosclerosis and lacunar infarcts through the pathway of ICAD. Presenting hypertension indirectly increased the odds of displaying hyaline arteriolosclerosis by 26 % (95 % CI: 1.08, 1.45, p = 0.002) and lacunar infarcts by 17 % (95 % CI: 1.01, 1.35, p = 0.029). Cognitive and APOE ε4 carrier status did not alter the investigated associations. In this community sample, hypertension was indirectly associated with cSVD through ICAD.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"145 ","pages":"Pages 84-95"},"PeriodicalIF":3.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624627","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 neural implementation of cognitive reserve: Insights from a longitudinal fMRI study of set-switching in aging","authors":"Fatemeh Hasanzadeh ,&nbsp;Christian Habeck ,&nbsp;Yunglin Gazes ,&nbsp;Yaakov Stern","doi":"10.1016/j.neurobiolaging.2024.10.008","DOIUrl":"10.1016/j.neurobiolaging.2024.10.008","url":null,"abstract":"<div><div>Aging is often accompanied by changes in brain structure and executive functions, particularly in tasks involving cognitive flexibility, such as task-switching. However, substantial individual differences in the degree of cognitive impairment indicate that some individuals can cope with brain changes more effectively than others, suggesting higher cognitive reserve (CR). This study identified a neural basis for CR by examining the longitudinal relationship between task-related brain activation, structural brain changes, and changes in cognitive performance during an executive task-switching paradigm including single and dual conditions. Fifty-two older individuals were assessed at baseline and followed up after five years. Structural brain changes related to task-switching performance were analyzed using elastic net regression. Task-related functional brain activation was measured using ordinal trends canonical variate analysis (OrT CVA), capturing patterns of activation increasing from single to dual conditions. A differential task-related expression score (dOrT) was calculated as the difference in pattern expression scores between single and dual conditions at baseline. A linear regression model tested whether dOrT moderated the impact of brain changes on changes in switch cost over five years. Results showed a significant interaction between changes in brain structure and dOrT activation on switch cost change, indicating a moderation effect of task-related activation. Higher dOrT buffered the impact of brain structural decline on switch costs, enabling older adults to better cope with age-related brain structural changes and preserve cognitive flexibility. These findings suggest that these task-related activation patterns represent a neural basis for CR.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"145 ","pages":"Pages 76-83"},"PeriodicalIF":3.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592857","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":"M1 muscarinic receptor activation reverses age-related memory updating impairment in mice","authors":"Kristen H. Jardine ,&nbsp;Emily P. Minard ,&nbsp;Cassidy E. Wideman ,&nbsp;Haley Edwards ,&nbsp;Karim H. Abouelnaga ,&nbsp;William S. Messer ,&nbsp;Boyer D. Winters","doi":"10.1016/j.neurobiolaging.2024.10.007","DOIUrl":"10.1016/j.neurobiolaging.2024.10.007","url":null,"abstract":"<div><div>Previously consolidated memories can become temporarily labile upon reactivation. Reactivation-based memory updating is chiefly studied in young subjects, so we aimed to assess this process across the lifespan. To do this, we developed a behavioural paradigm wherein a reactivated object memory is updated with contextual information; 3-month-old and 6-month-old male C57BL/6 mice displayed object memory updating, but 12-month-old mice did not. We found that M1 muscarinic acetylcholine receptor signaling during reactivation was necessary for object memory updating in the young mice. Next, we targeted this mechanism in an attempt to facilitate object memory updating in aging mice. Remarkably, systemic pharmacological M1 receptor activation reversed the age-related deficit. Quantification of cholinergic system markers within perirhinal cortex revealed subtle cellular changes that may contribute to differential performance across age groups. These findings suggest that natural cholinergic change across the lifespan contributes to inflexible memory in the aging brain.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"145 ","pages":"Pages 65-75"},"PeriodicalIF":3.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569328","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":"Exploring the links among brain iron accumulation, cognitive performance, and dietary intake in older adults: A longitudinal MRI study","authors":"Valentinos Zachariou ,&nbsp;Colleen Pappas ,&nbsp;Christopher E. Bauer ,&nbsp;Elayna R. Seago ,&nbsp;Brian T. Gold","doi":"10.1016/j.neurobiolaging.2024.10.006","DOIUrl":"10.1016/j.neurobiolaging.2024.10.006","url":null,"abstract":"<div><div>This study evaluated longitudinal brain iron accumulation in older adults, its association with cognition, and the role of specific nutrients in mitigating iron accumulation. MRI-based, quantitative susceptibility mapping estimates of brain iron concentration were acquired from seventy-two healthy older adults (47 women, ages 60–86) at a baseline timepoint (TP1) and a follow-up timepoint (TP2) 2.5–3.0 years later. Dietary intake was evaluated at baseline using a validated questionnaire. Cognitive performance was assessed at TP2 using the uniform data set (Version 3) neuropsychological tests of episodic memory (MEM) and executive function (EF). Voxel-wise, linear mixed-effects models, adjusted for longitudinal gray matter volume alterations, age, and several non-dietary lifestyle factors revealed brain iron accumulation in multiple subcortical and cortical brain regions, which was negatively associated with both MEM and EF performance at T2. However, consumption of specific dietary nutrients at TP1 was associated with reduced brain iron accumulation. Our study provides a map of brain regions showing iron accumulation in older adults over a short 2.5-year follow-up and indicates that certain dietary nutrients may slow brain iron accumulation.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"145 ","pages":"Pages 1-12"},"PeriodicalIF":3.7,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504777","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":"Amyloid pathology and cognitive impairment in hAβ-KI and APPSAA-KI mouse models of Alzheimer's disease","authors":"Wenyan Lu,&nbsp;Francis Shue,&nbsp;Aishe Kurti,&nbsp;Suren Jeevaratnam,&nbsp;Jesse R. Macyczko,&nbsp;Bhaskar Roy,&nbsp;Taha Izhar,&nbsp;Ni Wang,&nbsp;Guojun Bu ,&nbsp;Takahisa Kanekiyo,&nbsp;Yonghe Li","doi":"10.1016/j.neurobiolaging.2024.10.005","DOIUrl":"10.1016/j.neurobiolaging.2024.10.005","url":null,"abstract":"<div><div>The hAβ-KI and APP^SAA-KI are two amyloid models that harbor mutations in the endogenous mouse <em>App</em> gene. Both hAβ-KI and APP^SAA-KI mice contain a humanized Aβ sequence, and APP^SAA-KI mice carry three additional familial AD mutations. We herein report that the Aβ levels and Aβ42/Aβ40 ratio in APP^SAA-KI homozygotes are dramatically higher than those in hAβ-KI homozygotes at 14 months of age. In addition, APP^SAA-KI mice display a widespread distribution of amyloid plaques in the brain, whereas the plaques are undetectable in hAβ-KI mice. Moreover, there are no sex differences in amyloid pathology in APP^SAA-KI mice. Both APP^SAA-KI and hAβ-KI mice exhibit cognitive impairments, wherein no significant differences are found between these two models, although APP^SAA KI mice show a trend towards worse cognitive function. Notably, female hAβ-KI and APP^SAA-KI mice have a more pronounced cognitive impairments compared to their respective males. Our findings suggest that Aβ humanization contributes to cognitive deficits in APP^SAA-KI mice, and that amyloid deposition might not be closely associated with cognitive impairments in APP^SAA-KI mice.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"145 ","pages":"Pages 13-23"},"PeriodicalIF":3.7,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504776","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":"Longitudinal relationships between Aβ and tau to executive function and memory in cognitively normal older adults","authors":"Xi Chen ,&nbsp;Alexis Juarez ,&nbsp;Suzanne Mason ,&nbsp;Sarah Kobayashi ,&nbsp;Suzanne L. Baker ,&nbsp;Theresa M. Harrison ,&nbsp;Susan M. Landau ,&nbsp;William J. Jagust","doi":"10.1016/j.neurobiolaging.2024.10.004","DOIUrl":"10.1016/j.neurobiolaging.2024.10.004","url":null,"abstract":"<div><div>The early accumulation of AD pathology such as Aβ and tau in cognitively normal older people is predictive of cognitive decline, but it has been difficult to dissociate the cognitive effects of these two proteins. Early Aβ and tau target distinct brain regions that have different functional roles. Here, we assessed specific longitudinal pathology-cognition associations in seventy-six cognitively normal older adults from the Berkeley Aging Cohort Study who underwent longitudinal PiB PET, FTP PET, and cognitive assessments. Using linear mixed-effects models to estimate longitudinal changes and residual approach to characterizing cognitive domain-specific associations, we found that Aβ accumulation, especially in frontal/parietal regions, was associated with faster decline in executive function, not memory, whereas tau accumulation, especially in left entorhinal/parahippocampal regions, was associated with faster decline in memory, not executive function, supporting an “Aβ-executive function, tau-memory” double-dissociation in cognitively normal older people. These specific relationships between accumulating pathology and domain-specific cognitive decline may be due to the particular vulnerabilities of the frontal-parietal executive network to Aβ and temporal memory network to tau.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"145 ","pages":"Pages 32-41"},"PeriodicalIF":3.7,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142528427","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(24)00176-3","DOIUrl":"10.1016/S0197-4580(24)00176-3","url":null,"abstract":"","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"144 ","pages":"Page IFC"},"PeriodicalIF":3.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446246","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}