Integrative mapping of spatial transcriptomic and amyloid pathology in Alzheimer's disease at single-cell resolution
Zhang, G.-W.; Xia, S.; Zhang, N. K.; Gao, F.; Zlokovic, B. V.; Zhang, L. I.; Zhao, Z.; Tao, H.
Show abstract
Alzheimers disease (AD) is a complex neurodegenerative disorder that affects millions of people worldwide. Despite decades of research, the underlying molecular and cellular changes of AD remain unresolved, especially in terms of the spatial structure of gene expression changes that correlates with pathology, e.g. amyloid beta (A-beta) plaques. Recent advances in imaging-or sequencing-based single-cell spatial transcriptomics have allowed a systematic dissection of molecular and cell architectures in the brain and other tissues. In this study, we employed the recently developed Stereo-seq technology to spatially profile the whole-genome transcriptomics in the 5xFAD mouse model and established the methodology to analyze the specific neuronal transcriptomic changes spatially correlated with amyloid pathology at single cell resolution. More specifically, we developed a pipeline for integrative image- and non-image-based cell segmentation, VoxelMorph-based non-linear alignment, and Unet-based object detection to achieve reliable transcriptomics analysis at the single-cell resolution, and investigated the spatial relationship between diverse neuronal clusters and A-beta depositions. This work has demonstrated the potential of using the Stereo-seq technology as a powerful tool to investigate AD and other complex neurological disorders.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Gene module-trait network analysis uncovers cell type specific systems and genes relevant to Alzheimers Disease 94%
- Spatially resolved transcriptomics reveals unique gene signatures associated with human temporal cortical architecture and Alzheimer's pathology 93%
- Single-cell Spatial Proteomic Imaging for Human Neuropathology 92%
Similar papers in this journal
- mRNA-decapping associated DcpS enzyme controls critical steps of neuronal development 92%
- Early retinal deprivation crossmodally alters nascent subplate circuits and activity in the auditory cortex during the precritical period 91%
- Knock-down of hippocampal DISC1 in immune-challenged mice impairs the prefrontal-hippocampal coupling and the cognitive performance throughout development 91%
Similar papers in this journal
- An Experimental Platform for Stochastic Analyses of Single Serotonergic Fibers in the Mouse Brain 93%
- Optical spike detection and connectivity analysis with a far-red voltage-sensitive fluorophore reveals changes to network connectivity in development and disease 92%
- The therapeutic and diagnostic potential of amyloid β oligomers (AβOs) selective antibodies to treat Alzheimer's disease 92%
Similar papers in this journal
- Detecting the effect of genetic diversity on brain composition in an Alzheimer's disease mouse model 94%
- Essential roles of plexin-B3+ oligodendrocyte precursor cells in the pathogenesis of Alzheimer's disease 92%
- Functional brain region-specific neural spheroids for modeling neurological diseases and therapeutics screening 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.