PLX054888

GSE152506: Spatial Transcriptomics and In Situ Sequencing to Study Alzheimers Disease

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

While complex inflammatory-like alterations are observed around the amyloid plaques of Alzheimer disease (AD), little is known about the molecular changes and cellular interactions that characterize this response. We investigate here in an AD mouse model the transcriptional changes occurring in tissue domains of 100 m diameter around the amyloid plaques using spatial transcriptomics. We demonstrate early alterations in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIG), while a multicellular gene co- expression network of Plaque-Induced Genes (PIGs) involving the complement system, oxidative stress, lysosomes and inflammation is prominent in the later phase of the disease. We confirm the majority of the observed alterations at the cellular level using in situ sequencing on mouse and human brain sections. Genome-wide spatial transcriptomic analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases. SOURCE: Bart De Strooper (bart.destrooper@kuleuven.vib.be) - Laboratory for the research of neurodegenerative diseases VIB - KU Leuven