Aging brain最新文献_第6页

Glial cell transcriptome analyses in 3xTg-AD mice: Effects of aging, disease progression, and anti-Aβ immunotherapy 3xTg-AD小鼠的神经胶质细胞转录组分析:衰老、疾病进展和抗β免疫治疗的影响

Aging brain Pub Date : 2023-01-01 DOI: 10.1016/j.nbas.2023.100066

Doris Lambracht-Washington , Min Fu , Navid Manouchehri , Linda S. Hynan , Olaf Stuve , Roger N. Rosenberg

{"title":"Glial cell transcriptome analyses in 3xTg-AD mice: Effects of aging, disease progression, and anti-Aβ immunotherapy","authors":"Doris Lambracht-Washington , Min Fu , Navid Manouchehri , Linda S. Hynan , Olaf Stuve , Roger N. Rosenberg","doi":"10.1016/j.nbas.2023.100066","DOIUrl":"10.1016/j.nbas.2023.100066","url":null,"abstract":"<div><h3>Background</h3><p>To investigate how changes in expression of glial genes relate to a progression of Alzheimer’s disease (AD) pathology, and how anti-Aβ immunotherapy impact these changes, we conducted a transcriptomic analysis for brains from cohorts of 2-, 10-, and 20 month old 3xTg-AD mice, and a cross-sectional study in groups of 20 month-old mice treated with active DNA Aβ42 immunization, passive immunotherapy, untreated, and wild-type (wt) controls.</p></div><div><h3>Methods</h3><p>Twenty-four Formalin-Fixed Paraffin-Embedded (FFPE) mouse brain sections were used for the gene expression analyses (nanostring). Adjacent sections from these and additional mouse brains were stained for microglia using antibodies detecting IbaI and Gal3. For a semi-quantitative analysis of increased tau and amyloid pathology with aging and disease progression, a comparison of ELISA results from brains of 12 and 20 months old 3xTg-AD mice were shown.</p></div><div><h3>Results</h3><p>Based on the different comparisons of transcript numbers found the 3xTg-AD age groups with the senescent 20 months old wt control mouse brains, and the 20 months old 3xTg-AD mouse brains with the 20 months old wt control mouse brains, genes were assigned as upregulated due to aging, or due to disease progression, or due to both. The immunohistochemistry of microglia markers revealed that Gal3 might be an important marker for phagocytosing microglia around amyloid plaques. The comparison of the two anti-Aβ immunotherapy approaches showed a differential downregulation of inflammatory glial genes.</p></div><div><h3>Conclusion</h3><p>These results are relevant for future clinical trials using active anti-amyloid immunotherapy.</p></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"3 ","pages":"Article 100066"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f3/6f/main.PMC9997156.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9471623","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

The 5XFAD mouse model of Alzheimer’s disease displays age-dependent deficits in habituation to a novel environment 阿尔茨海默病的5XFAD小鼠模型显示出对新环境适应的年龄依赖性缺陷

Aging brain Pub Date : 2023-01-01 DOI: 10.1016/j.nbas.2023.100078

Sabrina Smith , Sarah C. Hopp

{"title":"The 5XFAD mouse model of Alzheimer’s disease displays age-dependent deficits in habituation to a novel environment","authors":"Sabrina Smith , Sarah C. Hopp","doi":"10.1016/j.nbas.2023.100078","DOIUrl":"10.1016/j.nbas.2023.100078","url":null,"abstract":"<div><p>Habituation is a form of learning characterized by a decrement in responsiveness to a stimulus that is repeated or prolonged. In rodents, habituation to a novel environment is characterized by a decrease in locomotion over time spent in a novel environment. Habituation to a novel environment is dependent on hippocampal function, suggesting that habituation behavior may be a relevant readout for hippocampal-dependent memory deficits that are characteristic of Alzheimer’s disease (AD). Current assays that measure hippocampal-dependent memory in preclinical animal models of AD have not accurately predicted the cognitive protection of novel interventions in human trials. Here, we tested whether a behavioral habituation paradigm could detect age-associated changes in a common preclinical mouse model of AD-like amyloid pathology, the 5XFAD mouse. We exposed 5XFAD mice and age-matched wild-type (WT) littermates at 3, 6, and 9 months of age to a novel environment over two sessions separated by 24 h and measured their locomotion. WT mice habituated to the novel environment over time, while 5XFAD mice displayed age-dependent deficits in behavioral habituation. We replicated our results using publicly available open field data from 5XFAD and late-onset AD mouse models with TREM2*R47H and APOE4 mutations. Overall, we present behavioral habituation as a potentially sensitive task to assess age-associated behavioral deficits in 5XFAD mice and other mouse models of AD that could be used to test the preclinical efficacy of novel AD therapeutics.</p></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"3 ","pages":"Article 100078"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d7/1a/main.PMC10275951.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9904238","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

Regional serotonin terminal density in aging human brain: A [11C]DASB PET study 衰老人脑区域5 -羟色胺末端密度:A [11C]DASB PET研究

Aging brain Pub Date : 2023-01-01 DOI: 10.1016/j.nbas.2023.100071

Prabesh Kanel , Robert A. Koeppe , Vikas Kotagal , Stiven Roytman , Martijn L.T.M. Muller , Nicolaas I. Bohnen , Roger L. Albin

{"title":"Regional serotonin terminal density in aging human brain: A [11C]DASB PET study","authors":"Prabesh Kanel , Robert A. Koeppe , Vikas Kotagal , Stiven Roytman , Martijn L.T.M. Muller , Nicolaas I. Bohnen , Roger L. Albin","doi":"10.1016/j.nbas.2023.100071","DOIUrl":"https://doi.org/10.1016/j.nbas.2023.100071","url":null,"abstract":"<div><p>There are conflicting results regarding regional age-related changes in serotonin terminal density in human brain. Some imaging studies suggest age-related declines in serotoninergic terminals and perikarya. Other human imaging studies and post-mortem biochemical studies suggest stable brain regional serotoninergic terminal densities across the adult lifespan. In this cross-sectional study, we used [<sup>11</sup>C]3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile positron emission tomography to quantify brain regional serotonin transporter density in 46 normal subjects, ranging from 25 to 84 years of age. Both voxel-based analyses, using sex as a covariate, and volume-of-interest-based analyses were performed. Both analyses revealed age-related declines in [<sup>11</sup>C]3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile binding in numerous brain regions, including several neocortical regions, striatum, amygdala, thalamus, dorsal raphe, and other subcortical regions. Similar to some other neurotransmitter systems of subcortical origin, we found evidence of age-related declines in regional serotonin terminal density in both cortical and subcortical regions.</p></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"3 ","pages":"Article 100071"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49774774","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: 1

In the quest for the ideal sweetener: Aspartame exacerbates selected biomarkers in the fruit fly (Drosophila melanogaster) model of Alzheimer's disease more than sucrose 在寻找理想甜味剂的过程中:阿斯巴甜比蔗糖更能加剧阿尔茨海默病果蝇模型中选定的生物标志物

Aging brain Pub Date : 2023-01-01 DOI: 10.1016/j.nbas.2023.100090

Bukola Christiana Adedayo , Stephanie Tolulope Akinniyi , Opeyemi Babatunde Ogunsuyi , Ganiyu Oboh

{"title":"In the quest for the ideal sweetener: Aspartame exacerbates selected biomarkers in the fruit fly (Drosophila melanogaster) model of Alzheimer's disease more than sucrose","authors":"Bukola Christiana Adedayo , Stephanie Tolulope Akinniyi , Opeyemi Babatunde Ogunsuyi , Ganiyu Oboh","doi":"10.1016/j.nbas.2023.100090","DOIUrl":"https://doi.org/10.1016/j.nbas.2023.100090","url":null,"abstract":"<div><p>This study evaluated the effect of dietary inclusions of aspartame and sucrose on some selected behavioral and biochemical indices linked with Alzheimer's disease in a transgenic fruit fly (Drosophila melanogaster) model expressing human amyloid precursor protein and secretase. Flies were raised on a diet supplemented with sucrose and aspartame for 14 days. Thereafter, the flies were assessed for their survival rate, learning and memory, as well as locomotor performance, 14 days post-treatment. This was followed by homogenising the fly heads, and the homogenates were assayed for acetylcholinesterase and monoamine oxidase activities, as well as levels of lipid peroxidation, reactive oxygen species, and total thiol. The results showed aspartame at all levels of dietary intake and a high proportion of sucrose significantly aggravated the mortality rate, locomotor deficiency, and impaired biomarkers of oxidative stress and antioxidant status in the transgenic flies, while no significant effect was found on acetylcholinesterase activity or memory function. These findings therefore suggest that while low dietary inclusions of sucrose are tolerable under AD-like phenotypes in the flies, high inclusions of sucrose and all proportions of aspartame tested aggravated mortality rate, locomotion and oxidative stress in the flies.</p></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"4 ","pages":"Article 100090"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49858042","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

Upregulation of endocytic protein expression in the Alzheimer’s disease male human brain 阿尔茨海默病男性人脑内吞蛋白表达上调

Aging brain Pub Date : 2023-01-01 DOI: 10.1016/j.nbas.2023.100084

Mouhamed Alsaqati , Rhian S. Thomas , Emma J. Kidd

{"title":"Upregulation of endocytic protein expression in the Alzheimer’s disease male human brain","authors":"Mouhamed Alsaqati , Rhian S. Thomas , Emma J. Kidd","doi":"10.1016/j.nbas.2023.100084","DOIUrl":"10.1016/j.nbas.2023.100084","url":null,"abstract":"<div><p>Amyloid-beta (Aβ) is produced from amyloid precursor protein (APP) primarily after APP is internalised by endocytosis and clathrin-mediated endocytic processes are altered in Alzheimer’s disease (AD). There is also evidence that cholesterol and flotillin affect APP endocytosis. We hypothesised that endocytic protein expression would be altered in the brains of people with AD compared to non-diseased subjects which could be linked to increased Aβ generation. We compared protein expression in frontal cortex samples from men with AD compared to age-matched, non-diseased controls. Soluble and insoluble Aβ40 and Aβ42, the soluble Aβ42/Aβ40 ratio, βCTF, BACE1, presenilin-1 and the ratio of phosphorylated:total GSK3β were significantly increased while the insoluble Aβ42:Aβ40 ratio was significantly decreased in AD brains. Total and phosphorylated tau were markedly increased in AD brains. Significant increases in clathrin, AP2, PICALM isoform 4, Rab-5 and caveolin-1 and 2 were seen in AD brains but BIN1 was decreased. However, using immunohistochemistry, caveolin-1 and 2 were decreased. The results obtained here suggest an overall increase in endocytosis in the AD brain, explaining, at least in part, the increased production of Aβ during AD.</p></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"4 ","pages":"Article 100084"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/01/44/main.PMC10336166.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10180955","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

New insight into tau immunotherapy 对tau免疫疗法的新见解

Aging brain Pub Date : 2023-01-01 DOI: 10.1016/j.nbas.2023.100089

Sadashiva Pai

引用次数: 0

Cognitive resilience and severe Alzheimer’s disease neuropathology 认知弹性和严重阿尔茨海默病的神经病理学

Aging brain Pub Date : 2023-01-01 DOI: 10.1016/j.nbas.2023.100065

Narges Ahangari , Corinne E. Fischer , Tom A. Schweizer , David G. Munoz

{"title":"Cognitive resilience and severe Alzheimer’s disease neuropathology","authors":"Narges Ahangari , Corinne E. Fischer , Tom A. Schweizer , David G. Munoz","doi":"10.1016/j.nbas.2023.100065","DOIUrl":"10.1016/j.nbas.2023.100065","url":null,"abstract":"<div><p>Cognitive resilience in Alzheimer’s disease (AD) can be defined as retention of high cognition despite presence of considerable cerebral AD lesions. We sought to identify factors associated with this phenomenon.</p><p>Data were obtained from National Alzheimer’s Coordinating Centre (NACC) dataset. Subjects with severe AD neuropathology, based on National Institute on Aging–Reagan (NIA-Reagan) criteria, no other primary neuropathology, and a ≤ 2-year interval between last follow-up and death were included. Mini-mental status examination score ≥ 24 was used as a proxy for normal cognition.</p><p>In total, 654 cases were included; 59 (9%) were cognitively resilient. Multivariable logistic regression model showed that resilient participants were more educated, had a lower body mass index (BMI), were more likely to be lifetime/recent smoker or use an anticoagulant/antiplatelet agent, compared with cognitively impaired subjects.</p><p>In addition to expected protective factors such as higher education and lower BMI, our results showed that smoking (especially recent smoking) and anticoagulant/antiplatelet consumption are associated with resilience to clinical cognitive expression of severe AD pathology. Pharmacological approaches using this information might be explored for clinical AD amelioration.</p></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"3 ","pages":"Article 100065"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f5/a4/main.PMC9997171.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9471625","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: 1

Longitudinal trajectories of spectral power during sleep in middle-aged and older adults 中老年人睡眠时光谱功率的纵向轨迹

Aging brain Pub Date : 2023-01-01 DOI: 10.1016/j.nbas.2022.100058

Chenlu Gao , Michael K. Scullin

{"title":"Longitudinal trajectories of spectral power during sleep in middle-aged and older adults","authors":"Chenlu Gao , Michael K. Scullin","doi":"10.1016/j.nbas.2022.100058","DOIUrl":"10.1016/j.nbas.2022.100058","url":null,"abstract":"<div><p>Age-related changes in sleep appear to contribute to cognitive aging and dementia. However, most of the current understanding of sleep across the lifespan is based on cross-sectional evidence. Using data from the Sleep Heart Health Study, we investigated longitudinal changes in sleep micro-architecture, focusing on whether such age-related changes are experienced uniformly across individuals. Participants were 2,202 adults (age<sub>Baseline</sub> = 62.40 ± 10.38, 55.36 % female, 87.92 % White) who completed home polysomnography assessment at two study visits, which were 5.23 years apart (range: 4–7 years). We analyzed NREM and REM spectral power density for each 0.5 Hz frequency bin, including slow oscillation (0.5–1 Hz), delta (1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), sigma (12–15 Hz), and beta-1 (15–20 Hz) bands. Longitudinal comparisons showed a 5-year decline in NREM delta (p <.001) and NREM sigma power density (p <.001) as well as a 5-year increase in theta power density during NREM (p =.001) and power density for all frequency bands during REM sleep (ps < 0.05). In contrast to the notion that sleep declines linearly with advancing age, longitudinal trajectories varied considerably across individuals. Within individuals, the 5-year changes in NREM and REM power density were strongly correlated (slow oscillation: r = 0.46; delta: r = 0.67; theta r = 0.78; alpha r = 0.66; sigma: r = 0.71; beta-1: r = 0.73; ps < 0.001). The convergence in the longitudinal trajectories of NREM and REM activity may reflect age-related neural de-differentiation and/or compensation processes. Future research should investigate the neurocognitive implications of longitudinal changes in sleep micro-architecture and test whether interventions for improving key sleep micro-architecture features (such as NREM delta and sigma activity) also benefit cognition over time.</p></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"3 ","pages":"Article 100058"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9997163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9471626","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: 1

The prevalence of sleep loss and sleep disorders in young and old adults 年轻人和老年人睡眠不足和睡眠障碍的患病率

Aging brain Pub Date : 2023-01-01 DOI: 10.1016/j.nbas.2022.100057

Vibha Madan Jha

引用次数: 2

Integrative Precision Medicine for Dementia and Alzheimer's Diseases in Africa 非洲痴呆症和阿尔茨海默病的综合精准医学

Aging brain Pub Date : 2023-01-01 DOI: 10.1016/j.nbas.2023.100095

Abdullahi Tunde Aborode , Nike Jesutofunmi Idowu , Samuel Tundealao , Joseph Jaiyeola , Ezemba Constance Chinyere , Seto Charles Ogunleye , Mercy Olorunshola , Ogunware Adedayo Emmanuel

引用次数: 0