Identification of amyloid plaques in retinas from Alzheimer's patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model.
Identification of amyloid plaques in retinas from Alzheimer's patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model.
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DOI：
10.1016/j.neuroimage.2010.06.020
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发表时间：
2011-01
期刊：
影响因子：
5.7
通讯作者：
Farkas, Daniel L.
中科院分区：
文献类型：
--
作者：
Koronyo-Hamaoui, Maya;Koronyo, Yosef;Ljubimov, Alexander V.;Miller, Carol A.;Ko, MinHee K.;Black, Keith L.;Schwartz, Michal;Farkas, Daniel L.
关键词：
对β - 淀粉样蛋白（Aβ）斑块进行无创监测对于阿尔茨海默病（AD）的诊断和预后至关重要，Aβ斑块是AD的神经病理学特征。目前在活体患者和动物模型大脑中对Aβ斑块的可视化在特异性和分辨率方面存在局限性。如果疾病病理在视网膜有所体现，作为大脑延伸部分的视网膜就为AD的活体无创光学成像提供了一个有吸引力的靶点。我们在AD患者（n = 8）的死后眼球以及疑似早期病例（n = 5）中发现了视网膜Aβ斑块，这与大脑病理学和临床报告相符；在年龄匹配的非AD个体（n = 5）中未检测到斑块。在APPSWE/PS1ΔE9转基因小鼠（AD - Tg；n = 18）而非非转基因野生型小鼠（n = 10）中，在全身给予姜黄素（一种安全的斑块标记荧光染料）后检测到了视网膜Aβ斑块。此外，视网膜斑块比在大脑中更早被检测到，并且随着疾病进展而累积。一种基于免疫的疗法在减少大脑斑块方面有效，免疫组与非免疫组AD小鼠相比（每组n = 4只小鼠），视网膜Aβ斑块负荷显著降低。在活体AD - Tg小鼠（n = 24）中，全身给予姜黄素能够在体内对视网膜Aβ斑块进行高分辨率和特异性的无创光学成像；在非转基因野生型小鼠（n = 11）中未检测到斑块。我们在AD患者视网膜中发现Aβ特异性斑块，以及在活体AD小鼠中无创检测单个视网膜斑块的能力，为开发用于早期AD诊断、预后评估和治疗反应的高分辨率光学成像奠定了基础。
Noninvasive monitoring of β-amyloid (Aβ) plaques, the neuropathological hallmarks of Alzheimer's disease (AD), is critical for AD diagnosis and prognosis. Current visualization of Aβ plaques in brains of live patients and animal models is limited in specificity and resolution. The retina as an extension of the brain portrays an appealing target for a live, noninvasive optical imaging of AD if disease pathology is manifested there. We identified retinal Aβ plaques in postmortem eyes from AD patients (n=8) and in suspected early stage cases (n=5), consistent with brain pathology and clinical reports; plaques were undetectable in age-matched non-AD individuals (n=5). In APPSWE/PS1ΔE9 transgenic mice (AD-Tg; n=18) and not in non-Tg wt mice (n=10), retinal Aβ plaques were detected following systemic administration of curcumin, a safe plaque-labeling fluorochrome. Moreover, retinal plaques were detectable earlier than in the brain and accumulated with disease progression. An immune-based therapy effective in reducing brain plaques, significantly reduced retinal Aβ plaque burden in immunized versus non-immunized AD mice (n=4 mice per group). In live AD-Tg mice (n=24), systemic administration of curcumin allowed noninvasive optical imaging of retinal Aβ plaques in vivo with high resolution and specificity; plaques were undetectable in non-Tg wt mice (n=11). Our discovery of Aβ specific plaques in retinas from AD patients, and the ability to noninvasively detect individual retinal plaques in live AD mice establish the basis for developing high resolution optical imaging for early AD diagnosis, prognosis assessment and response to therapies.
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影响因子：
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