Identification of Multicolor Fluorescent Probes for Heterogeneous Aβ Deposits in Alzheimer's Disease.
Identification of Multicolor Fluorescent Probes for Heterogeneous Aβ Deposits in Alzheimer's Disease.
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DOI：
10.3389/fnagi.2021.802614
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发表时间：
2021
影响因子：
4.8
通讯作者：
Soto C
中科院分区：
文献类型：
--
作者：
Mukherjee A;Al-Lahham R;Corkins ME;Samanta S;Schmeichel AM;Singer W;Low PA;Govindaraju T;Soto C
β 淀粉样蛋白 (Aβ) 积聚成淀粉样斑块，以及过度磷酸化的 tau 蛋白积聚成神经原纤维缠结 (NFT) 是阿尔茨海默病 (AD) 的病理标志。 Aβ 聚集体的形态和构象存在显着的个体内和个体间差异，这可能部分解释了 AD 中观察到的广泛临床和病理生理学异质性。在这项研究中，我们试图鉴定一系列荧光染料来特异性探测 Aβ 聚集体，以解决其多样性问题。我们筛选了一个小型荧光探针库，并鉴定了三种苯并噻唑-香豆素衍生物，它们对 AD 脑切片中的血管和实质 Aβ 沉积物进行了染色。这三种染料的组合可以使 Aβ 沉积物以三种不同的颜色（蓝色、绿色和远红色）可视化。重要的是，其中两种染料特异性地对 Aβ 沉积物进行染色，而对过度磷酸化的 tau 蛋白或 α-突触核蛋白沉积物没有明显的染色。此外，这组染料表现出与同一受试者中存在的不同类型的 Aβ 沉积物存在不同的相互作用。本研究中鉴定的 Aβ 聚集体特异性染料有可能进一步开发为用于诊断 AD 的 Aβ 成像探针。此外，我们在本研究中鉴定的远红染料可以作为小动物 Aβ 病理学成像的成像探针。最后，这些染料的组合可以帮助我们加深对各种 Aβ 沉积物与 AD 中观察到的临床多样性之间关系的理解。
Accumulation of amyloid-beta (Aβ) into amyloid plaques and hyperphosphorylated tau into neurofibrillary tangles (NFTs) are pathological hallmarks of Alzheimer’s disease (AD). There is a significant intra- and inter-individual variability in the morphology and conformation of Aβ aggregates, which may account in part for the extensive clinical and pathophysiological heterogeneity observed in AD. In this study, we sought to identify an array of fluorescent dyes to specifically probe Aβ aggregates, in an effort to address their diversity. We screened a small library of fluorescent probes and identified three benzothiazole-coumarin derivatives that stained both vascular and parenchymal Aβ deposits in AD brain sections. The set of these three dyes allowed the visualization of Aβ deposits in three different colors (blue, green and far-red). Importantly, two of these dyes specifically stained Aβ deposits with no apparent staining of hyperphosphorylated tau or α-synuclein deposits. Furthermore, this set of dyes demonstrated differential interactions with distinct types of Aβ deposits present in the same subject. Aβ aggregate-specific dyes identified in this study have the potential to be further developed into Aβ imaging probes for the diagnosis of AD. In addition, the far-red dye we identified in this study may serve as an imaging probe for small animal imaging of Aβ pathology. Finally, these dyes in combination may help us advance our understanding of the relation between the various Aβ deposits and the clinical diversity observed in AD.
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影响因子：
12.7
作者：
Ikonomovic MD;Abrahamson EE;Price JC;Hamilton RL;Mathis CA;Paljug WR;Debnath ML;Cohen AD;Mizukami K;DeKosky ST;Lopez OL;Klunk WE
通讯作者：
Klunk WE
DOI：
10.1016/j.bbapap.2010.04.001
发表时间：
2010-07
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Biancalana M;Koide S
通讯作者：
Koide S
影响因子：
46.9
作者：
Hintersteiner, M;Enz, A;Gremlich, HU
通讯作者：
Gremlich, HU
影响因子：
17.1
作者：
Herrmann, Uli S.;Schuetz, Anne K.;Aguzzi, Adriano
通讯作者：
Aguzzi, Adriano
影响因子：
4
作者：
Aslund, Andreas;Sigurdson, Christina J.;Klingstedt, Therese;Grathwohl, Stefan;Bolmont, Tristan;Dickstein, Dara L.;Glimsdal, Eirik;Prokop, Stefan;Lindgren, Mikael;Konradsson, Peter;Holtzman, David M.;Hof, Patrick R.;Heppner, Frank L.;Gandy, Samuel;Jucker, Mathias;Aguzzi, Adriano;Hammarstrom, Per;Nilsson, K. Peter R.
通讯作者：
Nilsson, K. Peter R.