Characterization of transcriptomic changes in the neurovascular unit of Alzheimiers transgenic mouse models using digital spatial profiling
Kalari, K. R.; Kandimalla, K. K.; Thompson, K.
Show abstract
Alzheimers disease (AD) affects 40 million individuals globally and is characterized by the accumulation of amyloid-beta (A{beta}) proteins, which aggregate and form plaques. BBB dysfunction drives AD cerebrovascular pathology and BBB integrity is maintained by neurovascular unit (NVU). Specifically, within the NVU, the cerebral endothelial cells maintain vascular homeostasis. In this study, we isolated endothelial-enriched regions of interest (ROIs) using the Nanostring GeoMx digital spatial profiler and employed a deconvolution model to evaluate transcriptomic changes. We observed dysregulation of cellular signaling potentially disrupting the APP+ BBB integrity. Analysis of ligand-receptor pairings that are the foundation of the NVU intercellular signaling indicated that the endothelial vasculature completes a feedback loop with the NVU to the regulating astroctyes. Further, we identified potentially antagonistic signaling roles for opioid receptor species that should be further investigated for potential therapeutic targets. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=159 HEIGHT=200 SRC="FIGDIR/small/640886v2_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@d89b56org.highwire.dtl.DTLVardef@be2d96org.highwire.dtl.DTLVardef@1a2e7bforg.highwire.dtl.DTLVardef@1cdc9f_HPS_FORMAT_FIGEXP M_FIG C_FIG
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- InCytokine, an open-source software, reveals a TREM2 variant specific cytokine signature 95%
- Arginase Inhibition Supports Survival and Differentiation of Neuronal Precursors in Adult Alzheimer's Disease Mice 94%
- Mitochondrial small RNA alterations associated with increased lysosome activity in an Alzheimer's Disease Mouse Model uncovered by PANDORA-seq 94%
Similar papers in this journal
- DNA damage and senescence in the aging and Alzheimer's disease cortex are not uniformly distributed 93%
- Ladostigil attenuates the oxidative and ER stress in human neuroblast-like SH-SY5Y cells 93%
- MicroRNAs and mRNA Regulatory Network of Parenchymal Hematoma after Endovascular Mechanical Reperfusion for Acute Ischemic Stroke in Rat 92%
Similar papers in this journal
- Single-cell multimodal omics and directly reprogrammed neurons to probe reduced penetrance in Frontotemporal Dementia 95%
- Spatio-temporal dynamics of microglia phenotype in human and murine cSVD: impact of acute and chronic hypertensive states 95%
- Circular RNA detection identifies circPSEN1 alterations in brain specific to Autosomal Dominant Alzheimer Disease 94%
Similar papers in this journal
- Proteomic Profiling Reveals Age-Related Changes in Transporter Proteins in the Human Blood-Brain Barrier 95%
- Modest changes in Spi1 dosage reveal the potential for altered microglial function as seen in Alzheimers disease 95%
- Transcriptomic Changes in Oligodendrocyte Lineage Cells During the Juvenile to Adult Transition in the Mouse Corpus Callosum 95%
"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.