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Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease

Research group Huitinga
Publication year 2020
Published in Cell
Authors Wei-Ting Chen, Ashley Lu, Katleen Craessaerts, Benjamin Pavie, C. Sala Frigerio, Nikky Corthout, Xiaoyan Qian, Jana Laláková, Malte Kühnemund, Iryna Voytyuk, Leen Wolfs, Renzo Mancuso, Evgenia Salta, Sriram Balusu, An Snellinx, Sebastian Munck, Aleksandra Jurek, Jose Fernandez Navarro, Takaomi C Saido, I. Huitinga, Joakim Lundeberg, Mark Fiers, Bart De Strooper

Although complex inflammatory-like alterations are observed around the amyloid plaques of Alzheimer’s 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 in a 100-μm diameter around amyloid plaques using spatial transcriptomics. We demonstrate early alterations in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIGs), whereas 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 transcriptomics analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.

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