Inflammation, neurodegeneration and protein aggregation in the retina as ocular biomarkers for Alzheimer's disease in the 3xTg-AD mouse model.
Inflammation, neurodegeneration and protein aggregation in the retina as ocular biomarkers for Alzheimer's disease in the 3xTg-AD mouse model.
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DOI：
10.1038/s41419-018-0740-5
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发表时间：
2018-06-07
影响因子：
9
通讯作者：
Di Angelantonio S
中科院分区：
文献类型：
--
作者：
Grimaldi A;Brighi C;Peruzzi G;Ragozzino D;Bonanni V;Limatola C;Ruocco G;Di Angelantonio S
阿尔茨海默病(AD)是导致老年人痴呆的最常见原因。在阿尔茨海默病的发病机制中，两种神经毒性蛋白在中枢神经系统中聚集和积累起着关键作用：淀粉样β蛋白和过度磷酸化的tau。细胞外淀粉样β蛋白斑块和细胞内高磷酸化tau缠结的积聚，以及随之而来的神经元丢失，在任何认知损伤之前10-15年就开始了。除了认知和行为缺陷，在AD患者和一些AD转基因小鼠模型中也描述了感觉异常。视网膜可以被认为是一个简单的大脑模型，因为大脑的一些病理变化和治疗策略可能会被观察到或适用于视网膜。在这里，我们提出了新的视网膜生物标志物，可以预测AD的诊断，并帮助开始和后续可能的未来治疗。我们分析了三转基因AD小鼠模型(3xTg-AD)的视网膜组织在疾病进展过程中的病理特征。我们发现在3xTg-AD小鼠的视网膜神经节细胞层中存在淀粉样β斑块、tau缠结、神经变性和星形胶质细胞增生，这些小鼠已经处于症状前期。此外，症状前期小鼠的视网膜小胶质细胞显示出一种分支的抗炎表型，在疾病发展过程中，这种表型会切换到促炎症的表型，分支较少的表型变得具有神经毒性。我们假设视网膜是监测AD相关神经退变过程的窗口。
Alzheimer's disease (AD) is the most common cause of dementia in the elderly. In the pathogenesis of AD a pivotal role is played by two neurotoxic proteins that aggregate and accumulate in the central nervous system: amyloid beta and hyper-phosphorylated tau. Accumulation of extracellular amyloid beta plaques and intracellular hyper-phosphorylated tau tangles, and consequent neuronal loss begins 10–15 years before any cognitive impairment. In addition to cognitive and behavioral deficits, sensorial abnormalities have been described in AD patients and in some AD transgenic mouse models. Retina can be considered a simple model of the brain, as some pathological changes and therapeutic strategies from the brain may be observed or applicable to the retina. Here we propose new retinal biomarkers that could anticipate the AD diagnosis and help the beginning and the follow-up of possible future treatments. We analyzed retinal tissue of triple-transgenic AD mouse model (3xTg-AD) for the presence of pathological hallmarks during disease progression. We found the presence of amyloid beta plaques, tau tangles, neurodegeneration, and astrogliosis in the retinal ganglion cell layer of 3xTg-AD mice, already at pre-symptomatic stage. Moreover, retinal microglia in pre-symptomatic mice showed a ramified, anti-inflammatory phenotype which, during disease progression, switches to a pro-inflammatory, less ramified one, becoming neurotoxic. We hypothesize retina as a window through which monitor AD-related neurodegeneration process.
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影响因子：
7.1
作者：
Holtman IR;Raj DD;Miller JA;Schaafsma W;Yin Z;Brouwer N;Wes PD;Möller T;Orre M;Kamphuis W;Hol EM;Boddeke EW;Eggen BJ
通讯作者：
Eggen BJ
影响因子：
9.3
作者：
Fischer F;Martin G;Agostini HT
通讯作者：
Agostini HT
影响因子：
15.1
作者：
Chiasseu M;Alarcon-Martinez L;Belforte N;Quintero H;Dotigny F;Destroismaisons L;Vande Velde C;Panayi F;Louis C;Di Polo A
通讯作者：
Di Polo A
影响因子：
12.7
作者：
Breyhan, Henning;Wirths, Oliver;Bayer, Thomas A.
通讯作者：
Bayer, Thomas A.
影响因子：
9.3
作者：
Colton CA;Mott RT;Sharpe H;Xu Q;Van Nostrand WE;Vitek MP
通讯作者：
Vitek MP