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Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease
Wei-Ting Chen1, Ashley Lu1, Katleen Craessaerts1
1VIB Center for Brain & Disease Research, Leuven 3000, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute, Leuven 3000, Belgium.
Cell
|July 24, 2020
Summary
Alzheimer's disease (AD) research reveals early changes in myelin and oligodendrocyte genes near amyloid plaques. Later stages show inflammation, oxidative stress, and complement system activation, offering new insights into AD pathology.
Area of Science:
- Neuroscience
- Molecular Biology
- Genomics
Background:
- Alzheimer's disease (AD) is characterized by amyloid plaques, surrounded by complex inflammatory-like alterations.
- The precise molecular changes and cellular interactions in the immediate vicinity of these plaques remain poorly understood.
Purpose of the Study:
- To investigate the transcriptional changes and cellular interactions within a 100-μm diameter around amyloid plaques in an AD mouse model.
- To identify early and late molecular events associated with plaque pathology.
Main Methods:
- Spatial transcriptomics was employed to analyze gene expression in tissue domains surrounding amyloid plaques.
- In situ sequencing was used to validate findings at the cellular level in mouse and human brain sections.
Main Results:
- Early alterations in gene co-expression networks enriched for myelin and oligodendrocyte genes (OLIGs) were observed.
- A later-phase network of plaque-induced genes (PIGs) involving complement system, oxidative stress, lysosomes, and inflammation became prominent.
- Validation confirmed these transcriptomic alterations at the cellular level.
Conclusions:
- Spatial transcriptomics provides a powerful approach to dissecting the complex cellular and molecular network dysregulated around AD hallmarks.
- This study reveals distinct early and late molecular responses to amyloid plaques, implicating oligodendrocyte function and inflammatory pathways.
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