Amyloid Beta Immunoreactivity in the Retinal Ganglion Cell Layer of the Alzheimer's Eye
Amyloid Beta Immunoreactivity in the Retinal Ganglion Cell Layer of the Alzheimer's Eye
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DOI：
10.3389/fnins.2020.00758
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发表时间：
2020-07-31
影响因子：
4.3
通讯作者：
Matsubara, Joanne A.
中科院分区：
文献类型：
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作者：
Lee, Sieun;Jiang, Kailun;Matsubara, Joanne A.
阿尔茨海默病 (AD) 是最常见的痴呆症，占所有痴呆症的 60-70%。 AD 经常被诊断不足，并且只有在较晚、更晚期的阶段才被识别，并且这种诊断延迟被认为是众多不成功的 AD 治疗试验的一个促成因素。尽管 AD 尚无已知治愈方法，但早期诊断对于疾病管理和护理非常重要。 AD 的一个标志是大脑中含有淀粉样蛋白 (Aβ) 的老年神经炎斑块和由过度磷酸化 tau 蛋白组成的神经原纤维缠结的沉积。然而，目前量化大脑中 Aβ 的体内方法是侵入性的，需要放射性示踪剂和正电子发射断层扫描。为了开发评估 AD 进展的替代方法，我们重点关注 AD 病理的视网膜表现。视网膜是中枢神经系统的延伸，具有独特的基于光的、非侵入性眼科成像的能力。然而，早期对人类视网膜的研究表明，文献对于 AD 视网膜中 Aβ 的存在存在分歧。为了帮助解决这一差异，本研究评估了经神经病理学证实的 AD 病例的视网膜组织，以确定 Aβ 在视网膜整体中的区域分布，并为未来针对 Aβ 的视网膜图像研究提供信息。同时还收集了死后脑组织。使用免疫组织化学、共聚焦显微镜和定量图像分析将包括神经炎斑块 (NP) 评分和脑淀粉样血管病 (CAA) 在内的神经病理学皮质评估与视网膜 Aβ 相关联。比较 AD 眼和对照（非 AD）眼的 β 负荷。我们的结果表明，AD 患者的细胞内和细胞外 Aβ 视网膜沉积物水平显着高于对照组。 AD 眼和对照眼的中周边 Aβ 水平均高于视网膜中央。在 AD 视网膜中，较高的细胞内 Aβ 与较低的 NP 评分相关，而较高的细胞外 Aβ 与较高的 CAA 评分相关。我们的数据支持使用视网膜组织评估眼部 Aβ 作为 AD 患者大脑中 Aβ 的替代测量的可行性。具体来说，中周边视网膜比中央视网膜拥有更多的Aβ沉积，因此可能是未来体内眼部成像的最佳位置。
Alzheimer's disease (AD) is the most prevalent form of dementia, accounting for 60-70% of all dementias. AD is often under-diagnosed and recognized only at a later, more advanced stage, and this delay in diagnosis has been suggested as a contributing factor in the numerous unsuccessful AD treatment trials. Although there is no known cure for AD, early diagnosis is important for disease management and care. A hallmark of AD is the deposition of amyloid-beta (A beta)-containing senile neuritic plaques and neurofibrillary tangles composed of hyperphosporylated tau in the brain. However, currentin vivomethods to quantify A beta in the brain are invasive, requiring radioactive tracers and positron emission tomography. Toward development of alternative methods to assess AD progression, we focus on the retinal manifestation of AD pathology. The retina is an extension of the central nervous system uniquely accessible to light-based, non-invasive ophthalmic imaging. However, earlier studies in human retina indicate that the literature is divided on the presence of A beta in the AD retina. To help resolve this disparity, this study assessed retinal tissues from neuropathologically confirmed AD cases to determine the regional distribution of A beta in retinal wholemounts and to inform on future retinal image studies targeting A beta. Concurrent post-mortem brain tissues were also collected. Neuropathological cortical assessments including neuritic plaque (NP) scores and cerebral amyloid angiopathy (CAA) were correlated with retinal A beta using immunohistochemistry, confocal microscopy, and quantitative image analysis. A beta load was compared between AD and control (non-AD) eyes. Our results indicate that levels of intracellular and extracellular A beta retinal deposits were significantly higher in AD than controls. Mid-peripheral A beta levels were greater than central retina in both AD and control eyes. In AD retina, higher intracellular A beta was associated with lower NP score, while higher extracellular A beta was associated with higher CAA score. Our data support the feasibility of using the retinal tissue to assess ocular A beta as a surrogate measure of A beta in the brain of individuals with AD. Specifically, mid-peripheral retina possesses more A beta deposition than central retina, and thus may be the optimal location for futurein vivoocular imaging.