Saving the "brain rainforest" in Alzheimer's disease: from single-node protection to ecosystem restoration

Abstract

The high failure rate of Alzheimer's disease (AD) drugs highlights the limitation of traditional single-target therapies for a disease with a heterogenous pathology. A recent study published in Cell by Li et al. pioneers a paradigm shift towards cell-type-directed combination therapy. By integrating snRNA-seq and real-world data, they repurposed letrozole and irinotecan and demonstrated that this combination effectively reverses multifaceted AD pathologies in mice.

Keywords

Alzheimer's disease / Combination therapy / Drug discovery / Targetome / Neurodegeneration

Ethical statements

Not applicable.

Author contributions

The authors confirm their contributions to the paper as follows: conceptualization: Zheng X, Hao H; writing of this manuscript: Zheng X, Hao H, Xia K, Relvas J; manuscript revision: Xia K, Relvas J. All authors reviewed the results and approved the final version of the manuscript.

Data availability

Not applicable.

Acknowledgements

This work was supported by the National Key Research and Development Program of China (grant 2021YFA1301300 to Haiping Hao) and the Natural Science Foundation of Jiangsu Province (grant BK20240095 to Xiao Zheng).

Conflict of interest

The authors declare that they have no conflict of interests.

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