Journal
CELL
Volume 182, Issue 4, Pages 976-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2020.06.038
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Funding
- INSTALZ (EU)
- EU Joint Program (JPND)
- Fonds voor Wetenschappelijk Onderzoek (FWO, Belgium)
- KU Leuven (Belgium)
- Stichting Alzheimer Onderzoek (Belgium)
- Alzheimer Association (USA)
- MRC (UK)
- Alzheimer Society (UK)
- Alzheimer Research UK
- VIB Tech Watch (Belgium)
- Knut and Alice Wallenberg Foundation (Sweden)
- Thon Foundation (Sweden)
- Taiwan Ministry of Science and Technology [MOST-105-2917-I-564-081]
- Marie Sklodowska-Curie [665501]
- FWO
- KUL
- European Research Council (EU) [ERC-CELL-PHASE_AD834682]
- Geneeskundige Stichting Koningin Elisabeth (Belgium)
- Bax-Vanluffelen (Belgium)
- MRC [UKDRI-1013, UKDRI-1004] Funding Source: UKRI
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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-mu m 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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