Cell-type-directed network-correcting combination therapy for Alzheimer’s disease. Yaqiao Li et al.

We organized and computationally integrated a comprehensive single nucleus RNA-sequencing (snRNA-seq) dataset by combining published data from three independent studies ( Mathys et al 2019., Zhou et al. 2020, and Lau et al. 2020). This integrated analysis enhanced patient representation, effectively corrected batch/technical artifacts, and improved consistency in DEG detection efficiency across cell types, enabling robust and unbiased downstream drug target screening using these cell-type-specific DEG profiles as inputs.

Single-nucleus RNA-sequencing analysis of the combination-treated (letrozole and irinotecan) and vehicle-treated mice confirmed that the combination therapy demonstrated beneficial effects transcriptomically, through increasing neuronal cell abundance, promoting neuroprotective functional pathways, and reversing disease-associated gene networks in a cell-type-specific manner.