Department of Clinical Sciences Malmö, Clinical Memory Research Unit, Lund University, Malmö, Sweden.
Department of Neurology, University of California, San Francisco, CA, USA.
J Alzheimers Dis. 2020;73(3):1201-1209. doi: 10.3233/JAD-190868.
Previous studies have used immunohistology to demonstrate Alzheimer's disease (AD) characteristic accumulation of amyloid-β (Aβ) in the retina of AD patients, a finding indicating retina examination as a potential diagnostic tool for AD pathology.
To further explore this idea by investigating whether levels of Aβ42 and Aβ40 in retina are associated with corresponding levels in hippocampus, neuropathological assessments, apolipoprotein E (APOE) genotype, and levels of islet amyloid polypeptide (IAPP).
Levels of high molecular weight (HMW) Aβ42, Aβ40, and IAPP in ultra-centrifuged homogenates of retina and hippocampus from patients with AD, multiple sclerosis, AD with Lewy bodies, and non-demented controls were analyzed using Mesoscale Discovery electrochemiluminescence technology employing immunoassay and enzyme-linked immunosorbent assay.
Higher levels of retinal and hippocampal Aβ42-HMW, Aβ40-HMW, and IAPP-HMW were found in individuals with high neuropathological scores of Aβ plaques and in individuals carrying the APOEɛ4 allele. The retinal levels of Aβ42-HMW and Aβ40-HMW correlated with corresponding levels in hippocampus as well as with neurofibrillary tangles (NFT) and Aβ scores. Retinal IAPP-HMW correlated with retinal levels of Aβ42-HMW and with NFT and Aβ scores.
These results show that different isoforms of Aβ can be detected in the human retina and moreover support the growing number of studies indicating that AD-related pathological changes occurring in the brain could be reflected in the retina.
先前的研究已经使用免疫组织化学技术证明了阿尔茨海默病(AD)患者视网膜中淀粉样蛋白-β(Aβ)的特征性积累,这一发现表明视网膜检查可能成为 AD 病理学的潜在诊断工具。
通过研究视网膜中 Aβ42 和 Aβ40 的水平是否与海马体、神经病理学评估、载脂蛋白 E(APOE)基因型以及胰岛淀粉样多肽(IAPP)的相应水平相关,进一步探讨这一观点。
使用 Mesoscale Discovery 电化学发光技术,通过免疫测定和酶联免疫吸附试验,分析 AD、多发性硬化症、AD 伴路易体和非痴呆对照患者的超离心匀浆中视网膜和海马体中高分子量(HMW)Aβ42、Aβ40 和 IAPP 的水平。
在 Aβ 斑块神经病理学评分较高和携带 APOEɛ4 等位基因的个体中,发现视网膜和海马体中 Aβ42-HMW、Aβ40-HMW 和 IAPP-HMW 的水平较高。视网膜 Aβ42-HMW 和 Aβ40-HMW 的水平与海马体相应水平以及神经原纤维缠结(NFT)和 Aβ 评分相关。视网膜 IAPP-HMW 与视网膜 Aβ42-HMW 以及 NFT 和 Aβ 评分相关。
这些结果表明,不同的 Aβ 同工型可以在人视网膜中检测到,并且支持越来越多的研究表明,大脑中发生的与 AD 相关的病理变化可能会反映在视网膜中。