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Model of brain maintenance reveals specific change-change association between medial-temporal lobe integrity and episodic memory 脑维持模型揭示了中颞叶完整性与情景记忆之间的特定变化-变化关联
Pub Date : 2022-01-01 DOI: 10.1016/j.nbas.2021.100027
Jarkko Johansson , Anders Wåhlin , Anders Lundquist , Andreas M. Brandmaier , Ulman Lindenberger , Lars Nyberg

Brain maintenance has been identified as a major determinant of successful memory aging. However, the extent to which brain maintenance in support of successful memory aging is specific to memory-related brain regions or forms part of a brain-wide phenomenon is unresolved. Here, we used longitudinal brain-wide gray matter MRI volumes in 262 healthy participants aged 55 to 80 years at baseline to investigate separable dimensions of brain atrophy, and explored the links of these dimensions to different dimensions of cognitive change. We statistically adjusted for common causes of change in both brain and cognition to reveal a potentially unique signature of brain maintenance related to successful memory aging. Critically, medial temporal lobe (MTL)/hippocampal change and episodic memory change were characterized by unique, residual variance beyond general factors of change in brain and cognition, and a reliable association between these two residualized variables was established (r = 0.36, p < 0.01). The present study is the first to provide solid evidence for a specific association between changes in (MTL)/hippocampus and episodic memory in normal human aging. We conclude that hippocampus-specific brain maintenance relates to the specific preservation of episodic memory in old age, in line with the notion that brain maintenance operates at both general and domain-specific levels.

大脑维护已被确定为成功记忆老化的主要决定因素。然而,大脑维护在多大程度上支持成功的记忆老化是特定于记忆相关的大脑区域,还是形成了全脑现象的一部分,这一点尚未得到解决。在这里,我们使用262名年龄在55 - 80 岁的健康参与者的纵向脑灰质MRI体积来研究脑萎缩的可分离维度,并探索这些维度与认知变化的不同维度之间的联系。我们对大脑和认知变化的常见原因进行了统计调整,以揭示与成功的记忆衰老相关的大脑维护的潜在独特特征。重要的是,内侧颞叶(MTL)/海马变化和情景记忆变化具有独特的特征,残差超出了大脑和认知变化的一般因素,并且这两个残差变量之间建立了可靠的关联(r = 0.36,p < 0.01)。目前的研究首次为正常人类衰老过程中(MTL)/海马体的变化与情景记忆之间的特定关联提供了确凿的证据。我们得出结论,海马体特异性大脑维护与老年情景记忆的特定保存有关,这与大脑维护在一般和特定领域水平上运作的概念一致。
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引用次数: 7
Aging entails distinct requirements for Rb at maintaining adult neurogenesis 衰老对Rb在维持成人神经发生方面有不同的要求
Pub Date : 2022-01-01 DOI: 10.1016/j.nbas.2022.100041
Saad Omais, Rouba N. Hilal, Nour N. Halaby, Carine Jaafar, Noël Ghanem

Cell cycle proteins play essential roles in regulating embryonic and adult neurogenesis in the mammalian brain. A key example is the Retinoblastoma protein (Rb) whose loss disrupts the whole neurogenic program during brain development, but only results in increased progenitor proliferation in the adult subventricular zone (SVZ) and compromised long-term neuronal survival in the adult olfactory bulb (OB). Whether this holds true of neurogenesis in the aged brain remains unknown. In this study, we find no evidence of irregular proliferation or early commitment defects in the mid-aged (12-month-old) and old-aged (20-month-old) SVZ following tamoxifen-inducible Rb knockout (Rb iKO) in mice. However, we highlight a striking defect in early maturation of Rb-deficient migrating neuroblasts along the rostral migratory stream (RMS), followed by massive decline in neuronal generation inside the aged OB. In the absence of Rb, we also show evidence of incomplete cell cycle re-entry (CCE) along with DNA damage in the young OB, while we find a similar trend towards CCE but no clear signs of DNA damage or neurodegenerative signatures (pTau or Synuclein accumulation) in the aged OB. However, such phenotype could be masked by the severe maturation defect reported above in addition to the natural decline in adult neurogenesis with age. Overall, we show that Rb is required to prevent CCE and DNA damage in adult-born OB neurons, hence maintain neuronal survival. Moreover, while loss of Rb alone is insufficient to trigger seeding of neurotoxic species, this study reveals age-dependent non-monotonic dynamics in regulating neurogenesis by Rb.

细胞周期蛋白在哺乳动物大脑的胚胎和成人神经发生中起着重要的调节作用。一个关键的例子是视网膜母细胞瘤蛋白(Rb),它的缺失破坏了大脑发育过程中的整个神经发生程序,但只导致成人室下区(SVZ)祖细胞增殖增加,并损害成人嗅球(OB)的长期神经元存活。这是否适用于老年大脑的神经发生尚不清楚。在本研究中,我们没有发现中年(12个月)和老年(20个月)小鼠在他莫昔芬诱导的Rb敲除(Rb iKO)后出现不规则增殖或早期承诺缺陷的证据。然而,我们强调突出的缺陷在早熟Rb-deficient成神经细胞迁移的吻侧迁移流(RMS),其次是大幅下降在神经元的一代老年人OB。在Rb缺席的情况下,我们也说明不完整的细胞周期重新与DNA损伤(CCE)年轻的OB,当我们找到一个类似的趋势CCE但是没有明确的迹象表明DNA损伤或神经退行性签名(pTau或积累-核蛋白)岁OB。然而,这种表型可能被上面报道的严重的成熟缺陷和成人神经发生随年龄的自然下降所掩盖。总的来说,我们发现Rb是防止成年OB神经元CCE和DNA损伤所必需的,从而维持神经元的存活。此外,虽然单独失去Rb不足以触发神经毒性物种的播种,但本研究揭示了Rb调节神经发生的年龄依赖性非单调动力学。
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引用次数: 1
Capillary function progressively deteriorates in prodromal Alzheimer’s disease: A longitudinal MRI perfusion study 前驱阿尔茨海默病毛细血管功能进行性恶化:纵向MRI灌注研究
Pub Date : 2022-01-01 DOI: 10.1016/j.nbas.2022.100035
Lasse S. Madsen , Rune B. Nielsen , Peter Parbo , Rola Ismail , Irene K. Mikkelsen , Hanne Gottrup , Leif Østergaard , David J. Brooks , Simon F. Eskildsen

Cardiovascular risk factors are associated with the development of Alzheimer’s disease (AD), and increasing evidence suggests that cerebral microvascular dysfunction plays a vital role in the disease progression. Using magnetic resonance imaging, we investigated the two-year changes of the cerebral microvascular blood flow in 11 mild cognitively impaired (MCI) patients with prodromal AD compared to 12 MCI patients without evidence of AD and 10 cognitively intact age-matched controls. The pAD-MCI patients displayed widespread deterioration in microvascular cerebral perfusion associated with capillary dysfunction. No such changes were observed in the other two groups, suggesting that the dysfunction in capillary perfusion is linked to the AD pathophysiology. The observed capillary dysfunction may limit local oxygenation in AD leading to downstream β-amyloid aggregation, tau hyperphosphorylation, neuroinflammation and neuronal dysfunction. The findings are in agreement with the capillary dysfunction hypothesis of AD, suggesting that increasing heterogeneity of capillary blood flow is a primary pathological event in AD.

心血管危险因素与阿尔茨海默病(AD)的发展有关,越来越多的证据表明,大脑微血管功能障碍在疾病进展中起着至关重要的作用。利用磁共振成像技术,我们研究了11例轻度认知障碍(MCI)伴有AD前驱症状的患者,与12例无AD证据的MCI患者和10例认知完整的年龄匹配对照组相比,两年内脑微血管血流的变化。pAD-MCI患者表现出广泛的微血管脑灌注恶化,并伴有毛细血管功能障碍。在其他两组中未观察到这种变化,提示毛细血管灌注功能障碍与AD的病理生理有关。观察到的毛细血管功能障碍可能限制AD的局部氧合,导致下游β-淀粉样蛋白聚集,tau过度磷酸化,神经炎症和神经元功能障碍。研究结果与阿尔茨海默病的毛细血管功能障碍假说一致,表明毛细血管血流异质性增加是阿尔茨海默病的主要病理事件。
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引用次数: 4
Cerebral topography of vesicular cholinergic transporter changes in neurologically intact adults: A [18F]FEOBV PET study 神经完整成人囊状胆碱能转运蛋白变化的大脑地形:[18F]FEOBV PET研究
Pub Date : 2022-01-01 DOI: 10.1016/j.nbas.2022.100039
Prabesh Kanel , Sygrid van der Zee , Carlos A. Sanchez-Catasus , Robert A. Koeppe , Peter J.H. Scott , Teus van Laar , Roger L. Albin , Nicolaas I. Bohnen

Acetylcholine plays a major role in brain cognitive and motor functions with regional cholinergic terminal loss common in several neurodegenerative disorders. We describe age-related declines of regional cholinergic neuron terminal density in vivo using the positron emission tomography (PET) ligand [18F](–)5-Fluoroethoxybenzovesamicol ([18F]FEOBV), a vesamicol analogue selectively binding to the vesicular acetylcholine transporter (VAChT). A total of 42 subjects without clinical evidence of neurologic disease (mean 50.55 [range 20–80] years, 24 Male/18 Female) underwent [18F]FEOBV brain PET imaging. We used SPM based voxel-wise statistical analysis to perform whole brain voxel-based parametric analysis (family-wise error corrected, FWE) and to also extract the most significant clusters of regions correlating with aging with gender as nuisance variable. Age-related VAChT binding reductions were found in primary sensorimotor cortex, visual cortex, caudate nucleus, anterior to mid-cingulum, bilateral insula, para-hippocampus, hippocampus, anterior temporal lobes/amygdala, dorsomedial thalamus, metathalamus, and cerebellum (gender and FWE-corrected, P < 0.05). These findings show a specific topographic pattern of regional vulnerability of cholinergic nerve terminals across multiple cholinergic systems accompanying aging.

乙酰胆碱在脑认知和运动功能中起重要作用,在一些神经退行性疾病中常见的区域性胆碱能终端丧失。我们使用正电子发射断层扫描(PET)配体[18F](-)5-氟乙氧基苯唑维氨醇([18F]FEOBV)描述了体内区域胆碱能神经元末端密度与年龄相关的下降,这是一种选择性结合囊泡乙酰胆碱转运体(VAChT)的维氨醇类似物。共有42例无神经系统疾病临床证据的受试者(平均50.55岁[范围20-80]岁,男24名/女18名)接受了[18F]FEOBV脑PET成像。我们使用基于SPM的体素统计分析来执行基于全脑体素的参数分析(family-wise error corrected, FWE),并提取与年龄相关的最显著的区域簇,将性别作为干扰变量。在初级感觉运动皮层、视觉皮层、尾状核、中扣带前部、双侧岛、海马旁、海马、前颞叶/杏仁核、丘脑背内侧、后丘脑和小脑中发现与年龄相关的VAChT结合减少(性别和fwe校正,P < 0.05)。这些发现表明,随着年龄的增长,胆碱能神经末梢在多个胆碱能系统中的区域易损具有特定的地形模式。
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引用次数: 11
Can the entorhinal cortex help distinguish healthy aging brains from pathological aging brains? 内嗅皮层能帮助区分健康老化的大脑和病理性老化的大脑吗?
Pub Date : 2022-01-01 DOI: 10.1016/j.nbas.2021.100026
Akihiko Takashima, Riki Koike, Yoshiyuki Soeda
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引用次数: 0
Physical activity moderates the association between executive function and functional connectivity in older adults 体育活动调节老年人执行功能和功能连接之间的关联
Pub Date : 2022-01-01 DOI: 10.1016/j.nbas.2022.100036
Marissa A Gogniat, Talia L Robinson, Kharine R Jean, L Stephen Miller

Recent evidence suggests that physical activity may influence the functional connectivity of the aging brain. The purpose of this study was to examine the influence of physical activity on the association between executive function and functional connectivity of key brain networks and graph theory metrics in community-dwelling older adults. Participants were 47 older adults (M = 73 years; SD = 5.92) who participated in neuropsychological testing, physical activity measurements, and magnetic resonance imaging (MRI). Seed-to-voxel moderation analyses and graph theory analyses were conducted. Physical activity was significantly positively associated with default mode network functional connectivity (DMN FC; Posterior Cingulate Gyrus, p-FDR = 0.005; Frontal Pole (L), p-FDR = 0.005; Posterior Cingulate Gyrus, p-FDR = 0.006; Superior Frontal Gyrus (L), p-FDR = 0.016) and dorsal attention network functional connectivity (DAN FC; Inferior Frontal Gyrus Pars Opercularis (R), p-FDR = 0.044). The interaction between physical activity and executive function on the DMN FC and DAN FC was analyzed. The interaction between executive function and physical activity was significantly associated with DMN FC. When this significant interaction was probed, the association between physical activity and DMN FC differed between levels of high and low executive function such that the association was only significant at levels of high executive function. These results suggest that greater physical activity in later life is associated with greater DMN and DAN FC and provides evidence for the importance of physical activity in cognitively healthy older adults.

最近的证据表明,体育活动可能会影响老化大脑的功能连接。本研究旨在探讨体力活动对社区居住老年人执行功能与关键脑网络功能连通性和图论指标之间关系的影响。参与者为47名老年人(M = 73 岁;SD = 5.92),他们参加了神经心理测试、身体活动测量和磁共振成像(MRI)。进行了种子到体素的调节分析和图论分析。体育活动与默认模式网络功能连通性(DMN FC)显著正相关;扣带后回,p-FDR = 0.005;额极(L), p-FDR = 0.005;扣带后回,p-FDR = 0.006;额上回(L), p-FDR = 0.016)和背侧注意网络功能连通性(DAN FC;额下回盖部(R), p-FDR = 0.044)。分析了运动与DMN和DAN FC执行功能的相互作用。执行功能和身体活动之间的相互作用与DMN FC显著相关。当这种显著的相互作用被探究时,体力活动和DMN FC之间的关联在高执行功能和低执行功能水平之间存在差异,因此这种关联仅在高执行功能水平上显着。这些结果表明,晚年更多的体育活动与更高的DMN和DAN FC有关,并为体育活动对认知健康的老年人的重要性提供了证据。
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引用次数: 4
Hemispheric dissociations in regions supporting auditory sentence comprehension in older adults 老年人支持听觉句子理解区域的半球分离
Pub Date : 2022-01-01 DOI: 10.1016/j.nbas.2022.100051
Yune Sang Lee , Chad S. Rogers , Murray Grossman , Arthur Wingfield , Jonathan E. Peelle

We investigated how the aging brain copes with acoustic and syntactic challenges during spoken language comprehension. Thirty-eight healthy adults aged 54 – 80 years (M = 66 years) participated in an fMRI experiment wherein listeners indicated the gender of an agent in short spoken sentences that varied in syntactic complexity (object-relative vs subject-relative center-embedded clause structures) and acoustic richness (high vs low spectral detail, but all intelligible). We found widespread activity throughout a bilateral frontotemporal network during successful sentence comprehension. Consistent with prior reports, bilateral inferior frontal gyrus and left posterior superior temporal gyrus were more active in response to object-relative sentences than to subject-relative sentences. Moreover, several regions were significantly correlated with individual differences in task performance: Activity in right frontoparietal cortex and left cerebellum (Crus I & II) showed a negative correlation with overall comprehension. By contrast, left frontotemporal areas and right cerebellum (Lobule VII) showed a negative correlation with accuracy specifically for syntactically complex sentences. In addition, laterality analyses confirmed a lack of hemispheric lateralization in activity evoked by sentence stimuli in older adults. Importantly, we found different hemispheric roles, with a left-lateralized core language network supporting syntactic operations, and right-hemisphere regions coming into play to aid in general cognitive demands during spoken sentence processing. Together our findings support the view that high levels of language comprehension in older adults are maintained by a close interplay between a core left hemisphere language network and additional neural resources in the contralateral hemisphere.

我们研究了老化的大脑在口语理解过程中如何应对声学和句法挑战。38名年龄在54 - 80 岁(M = 66 岁)的健康成年人参加了一项功能磁共振成像实验,在实验中,听者在句法复杂性(客体相对与主体相对的中心嵌入子句结构)和声学丰富性(高光谱细节与低光谱细节,但都是可理解的)不同的短口语句子中指出一个主体的性别。我们发现,在成功理解句子的过程中,双侧额颞叶网络普遍活跃。与先前的报道一致,双侧额下回和左侧颞后上回对客体相关句子的反应比对主体相关句子的反应更活跃。此外,有几个区域与任务表现的个体差异显著相关:右额顶叶皮层和左小脑的活动(小腿I &II)与整体理解呈负相关。相比之下,左侧额颞区和右侧小脑(第七小叶)与句法复杂句子的准确性呈负相关。此外,侧性分析证实了老年人在句子刺激引起的活动中缺乏半球侧化。重要的是,我们发现了不同半球的作用,左半球的核心语言网络支持句法操作,而右半球区域在口语句子处理过程中起作用,帮助一般认知需求。总之,我们的研究结果支持这样一种观点,即老年人的高水平语言理解是由左半球核心语言网络和对侧半球额外的神经资源之间的密切相互作用维持的。
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引用次数: 1
Age-related differences in white matter microstructure measured by advanced diffusion MRI in healthy older adults at risk for Alzheimer’s disease 在阿尔茨海默病风险的健康老年人中,高级扩散MRI测量的白质微结构的年龄相关差异
Pub Date : 2022-01-01 DOI: 10.1016/j.nbas.2022.100030
Alice Motovylyak , Nicholas M. Vogt , Nagesh Adluru , Yue Ma , Rui Wang , Jennifer M. Oh , Steven R. Kecskemeti , Andrew L. Alexander , Douglas C. Dean , Catherine L. Gallagher , Mark A. Sager , Bruce P. Hermann , Howard A. Rowley , Sterling C. Johnson , Sanjay Asthana , Barbara B. Bendlin , Ozioma C. Okonkwo

Neurite orientation dispersion and density imaging (NODDI) is an advanced diffusion imaging technique, which can detect more distinct microstructural features compared to conventional Diffusion Tensor Imaging (DTI). NODDI allows the signal to be divided into multiple water compartments and derive measures for orientation dispersion index (ODI), neurite density index (NDI) and volume fraction of isotropic diffusion compartment (FISO). This study aimed to investigate which diffusion metric—fractional anisotropy (FA), mean diffusivity (MD), NDI, ODI, or FISO—is most influenced by aging and reflects cognitive function in a population of healthy older adults at risk for Alzheimer’s disease (AD). Age was significantly associated with all but one diffusion parameters and regions of interest. NDI and MD in the cingulate region adjacent to the cingulate cortex showed a significant association with a composite measure of Executive Function and was proven to partially mediate the relationship between aging and Executive Function decline. These results suggest that both DTI and NODDI parameters are sensitive to age-related differences in white matter regions vulnerable to aging, particularly among older adults at risk for AD.

神经突定向弥散和密度成像(NODDI)是一种先进的扩散成像技术,与传统的扩散张量成像(DTI)相比,可以检测到更清晰的微结构特征。NODDI可以将信号划分为多个水区,并推导出取向弥散指数(ODI)、神经突密度指数(NDI)和各向同性扩散区体积分数(FISO)的测量方法。本研究旨在探讨哪一种扩散指标——分数各向异性(FA)、平均扩散率(MD)、NDI、ODI或fso——受年龄影响最大,并反映有阿尔茨海默病(AD)风险的健康老年人群体的认知功能。年龄与除一个扩散参数和感兴趣的区域外的所有扩散参数和区域显著相关。扣带皮层附近扣带区的NDI和MD与执行功能的综合测量有显著的关联,并被证明部分介导衰老和执行功能下降之间的关系。这些结果表明,DTI和NODDI参数对易衰老的白质区域的年龄相关差异很敏感,特别是在有AD风险的老年人中。
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引用次数: 6
Compromised autophagy and mitophagy in brain ageing and Alzheimer’s diseases 脑老化和阿尔茨海默病中的自噬和有丝自噬受损
Pub Date : 2022-01-01 DOI: 10.1016/j.nbas.2022.100056
Domenica Caponio , Kateřina Veverová , Shi-qi Zhang , Liu Shi , Garry Wong , Martin Vyhnalek , Evandro F. Fang

Alzheimer’s disease (AD) is one of the most persistent and devastating neurodegenerative disorders of old age, and is characterized clinically by an insidious onset and a gradual, progressive deterioration of cognitive abilities, ranging from loss of memory to impairment of judgement and reasoning. Despite years of research, an effective cure is still not available. Autophagy is the cellular ‘garbage’ clearance system which plays fundamental roles in neurogenesis, neuronal development and activity, and brain health, including memory and learning. A selective sub-type of autophagy is mitophagy which recognizes and degrades damaged or superfluous mitochondria to maintain a healthy and necessary cellular mitochondrial pool. However, emerging evidence from animal models and human samples suggests an age-dependent reduction of autophagy and mitophagy, which are also compromised in AD. Upregulation of autophagy/mitophagy slows down memory loss and ameliorates clinical features in animal models of AD. In this review, we give an overview of autophagy and mitophagy and their link to the progression of AD. We also summarize approaches to upregulate autophagy/mitophagy. We hypothesize that age-dependent compromised autophagy/mitophagy is a cause of brain ageing and a risk factor for AD, while restoration of autophagy/mitophagy to more youthful levels could return the brain to health.

阿尔茨海默病(AD)是一种最持久和最具破坏性的老年神经退行性疾病,其临床特点是发病隐匿,认知能力逐渐恶化,从记忆丧失到判断和推理能力受损。尽管经过多年的研究,仍然没有有效的治疗方法。自噬是细胞“垃圾”清除系统,在神经发生、神经元发育和活动以及大脑健康(包括记忆和学习)中起着重要作用。自噬的一个选择性亚型是线粒体自噬,它识别并降解受损或多余的线粒体,以维持健康和必要的细胞线粒体池。然而,来自动物模型和人类样本的新证据表明,自噬和有丝自噬的年龄依赖性减少,这在AD中也受到损害。自噬/有丝自噬的上调减缓了AD动物模型的记忆丧失并改善了临床特征。在这篇综述中,我们就自噬和有丝自噬及其与AD进展的关系进行综述。我们还总结了上调自噬/有丝自噬的方法。我们假设年龄依赖性受损的自噬/线粒体自噬是导致大脑老化的一个原因,也是AD的一个危险因素,而自噬/线粒体自噬恢复到更年轻的水平可以使大脑恢复健康。
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引用次数: 5
Cerebral Aβ deposition in an Aβ-precursor protein-transgenic rhesus monkey Aβ前体蛋白转基因恒河猴脑内Aβ沉积
Pub Date : 2022-01-01 DOI: 10.1016/j.nbas.2022.100044
Anthony W.S. Chan , In Ki Cho , Chun-Xia Li , Xiaodong Zhang , Sudeep Patel , Rebecca Rusnak , Jessica Raper , Jocelyne Bachevalier , Sean P. Moran , Tim Chi , Katherine H. Cannon , Carissa E. Hunter , Ryan C. Martin , Hailian Xiao , Shang-Hsun Yang , Sanjeev Gumber , James G. Herndon , Rebecca F. Rosen , William T. Hu , James J. Lah , Lary C. Walker

With the ultimate goal of developing a more representative animal model of Alzheimer's disease (AD), two female amyloid-β-(Aβ) precursor protein-transgenic (APPtg) rhesus monkeys were generated by lentiviral transduction of the APP gene into rhesus oocytes, followed by in vitro fertilization and embryo transfer. The APP-transgene included the AD-associated Swedish K670N/M671L and Indiana V717F mutations (APPSWE/IND) regulated by the human polyubiquitin-C promoter. Overexpression of APP was confirmed in lymphocytes and brain tissue. Upon sacrifice at 10 years of age, one of the monkeys had developed Aβ plaques and cerebral Aβ-amyloid angiopathy in the occipital, parietal, and caudal temporal neocortices. The induction of Aβ deposition more than a decade prior to its usual emergence in the rhesus monkey supports the feasibility of creating a transgenic nonhuman primate model for mechanistic analyses and preclinical testing of treatments for Alzheimer's disease and cerebrovascular amyloidosis.

以建立更具代表性的阿尔茨海默病(AD)动物模型为最终目标,通过慢病毒将APP基因转导到恒河猴卵母细胞中,产生两只雌性淀粉样蛋白-β-(a β)前体蛋白转基因(APPtg)恒河猴,然后进行体外受精和胚胎移植。app -转基因包括ad相关的瑞典K670N/M671L和印第安纳V717F突变(APPSWE/IND),由人多泛素- c启动子调控。APP在淋巴细胞和脑组织中均有过表达。在10 岁时牺牲时,其中一只猴子在枕叶、顶叶和尾叶颞新皮层出现了Aβ斑块和大脑Aβ-淀粉样血管病。在恒河猴中,a β沉积的诱导比通常的出现早10多年,这支持了创建转基因非人灵长类动物模型的可行性,用于机制分析和阿尔茨海默病和脑血管淀粉样变性治疗的临床前测试。
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引用次数: 2
期刊
Aging brain
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