Whole-brain microscopy reveals distinct temporal and spatial efficacy of anti-Aβ therapies.
Whole-brain microscopy reveals distinct temporal and spatial efficacy of anti-Aβ therapies.
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DOI：
10.15252/emmm.202216789
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发表时间：
2023-01-11
影响因子：
11.1
通讯作者：
Aguzzi, Adriano
中科院分区：
文献类型：
--
作者：
Kirschenbaum, Daniel;Dadgar-Kiani, Ehsan;Catto, Francesca;Voigt, Fabian F.;Trevisan, Chiara;Bichsel, Oliver;Shirani, Hamid;Nilsson, K. Peter R.;Frontzek, Karl J.;Paganetti, Paolo;Helmchen, Fritjof;Lee, Jin Hyung;Aguzzi, Adriano
Many efforts targeting amyloid‐β (Aβ) plaques for the treatment of Alzheimer's Disease thus far have resulted in failures during clinical trials. Regional and temporal heterogeneity of efficacy and dependence on plaque maturity may have contributed to these disappointing outcomes. In this study, we mapped the regional and temporal specificity of various anti‐Aβ treatments through high‐resolution light‐sheet imaging of electrophoretically cleared brains. We assessed the effect on amyloid plaque formation and growth in Thy1‐APP/PS1 mice subjected to β‐secretase inhibitors, polythiophenes, or anti‐Aβ antibodies. Each treatment showed unique spatiotemporal Aβ clearance, with polythiophenes emerging as a potent anti‐Aβ compound. Furthermore, aligning with a spatial‐transcriptomic atlas revealed transcripts that correlate with the efficacy of each Aβ therapy. As observed in this study, there is a striking dependence of specific treatments on the location and maturity of Aβ plaques. This may also contribute to the clinical trial failures of Aβ‐therapies, suggesting that combinatorial regimens may be significantly more effective in clearing amyloid deposition. The brain is highly compartmentalized with many distinct regions. It is unknown how drugs for treating Alzheimer's Disease (AD) work across brain regions and disease stages. We developed a technology to quantify the effects of different AD drugs throughout the brain at different time points.
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影响因子：
7.1
作者：
Balakrishnan K;Rijal Upadhaya A;Steinmetz J;Reichwald J;Abramowski D;Fändrich M;Kumar S;Yamaguchi H;Walter J;Staufenbiel M;Thal DR
通讯作者：
Thal DR
影响因子：
12.4
作者：
Brendel M;Jaworska A;Overhoff F;Blume T;Probst F;Gildehaus FJ;Bartenstein P;Haass C;Bohrmann B;Herms J;Willem M;Rominger A
通讯作者：
Rominger A
影响因子：
17.1
作者：
Herrmann, Uli S.;Schuetz, Anne K.;Aguzzi, Adriano
通讯作者：
Aguzzi, Adriano
DOI：
10.1073/pnas.1218402110
发表时间：
2013-06-11
影响因子：
11.1
作者：
Cohen, Samuel I. A.;Linse, Sara;Knowles, Tuomas P. J.
通讯作者：
Knowles, Tuomas P. J.
在细胞分辨率下全脑图的交互式框架。
影响因子：
25
作者：
Fürth D;Vaissière T;Tzortzi O;Xuan Y;Märtin A;Lazaridis I;Spigolon G;Fisone G;Tomer R;Deisseroth K;Carlén M;Miller CA;Rumbaugh G;Meletis K
通讯作者：
Meletis K