Label-free hyperspectral imaging and deep-learning prediction of retinal amyloid β-protein and phosphorylated tau.

Label-free hyperspectral imaging and deep-learning prediction of retinal amyloid β-protein and phosphorylated tau.
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DOI:
10.1093/pnasnexus/pgac164
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发表时间:
2022-09
期刊:
PNAS NEXUS
影响因子:
--
通讯作者:
Gao, Liang
Gao, Liang
中科院分区:
其他
文献类型:
--
作者:
Du, Xiaoxi;Koronyo, Yosef;Mirzaei, Nazanin;Yang, Chengshuai;Fuchs, Dieu-Trang;Black, Keith L.;Koronyo-Hamaoui, Maya;Gao, Liang

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阿尔茨海默病(AD)是老年人口的主要风险之一。AD的病理特征-淀粉样β蛋白(Aβ)和磷酸化tau (pTau)的异常沉积-已经在AD患者的视网膜中得到证实,包括轻度认知障碍(MCI)的前驱患者。Aβ病理,特别是淀粉样蛋白42-残基长异体(a - β42)的积累,被认为是AD的早期和特异性征兆,与牛头病一起,证实了AD的诊断。为了可视化视网膜Aβ和pTau,最先进的方法使用荧光。然而,施用造影剂使成像过程复杂化。为了从根本上解决这个问题,我们进行了离体研究,开发了一种无标记的高光谱成像方法来检测a β42和pS396-Tau的光谱特征,并预测了它们在视网膜横切面中的丰度。我们首次报道了pTau的光谱特征,并证明了基于深度学习的Aβ和pTau分布的准确预测。我们期望我们的发现将为无标签检测AD奠定基础。
Alzheimer’s disease (AD) is a major risk for the aging population. The pathological hallmarks of AD—an abnormal deposition of amyloid β-protein (Aβ) and phosphorylated tau (pTau)—have been demonstrated in the retinas of AD patients, including in prodromal patients with mild cognitive impairment (MCI). Aβ pathology, especially the accumulation of the amyloidogenic 42-residue long alloform (Aβ42), is considered an early and specific sign of AD, and together with tauopathy, confirms AD diagnosis. To visualize retinal Aβ and pTau, state-of-the-art methods use fluorescence. However, administering contrast agents complicates the imaging procedure. To address this problem from fundamentals, ex-vivo studies were performed to develop a label-free hyperspectral imaging method to detect the spectral signatures of Aβ42 and pS396-Tau, and predicted their abundance in retinal cross-sections. For the first time, we reported the spectral signature of pTau and demonstrated an accurate prediction of Aβ and pTau distribution powered by deep learning. We expect our finding will lay the groundwork for label-free detection of AD.
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