Studying amyloid pathology in an Alzheimer’s mouse model in spatial context

Dr. Peter Larson & Jeroen Aerts, PhD

Explore how to use a highly multiplexed and sensitive spatial analysis tool to decipher the molecular landscape of complex disease.
Hallmarks such as Aβ plaques and neurofibrillary tau tangles are key pathological events in Alzheimer’s disease (AD), however, we still do not fully understand the disease at the cellular level. For example, why some cells and brain regions are more vulnerable to pathology, and which molecular changes cells undergo as the pathology sets in. Single-cell RNA sequencing studies have shed light on the molecular changes at the cellular level. However, single-cell RNA sequencing studies lack the spatial context. Investigations of the transcriptomics changes that take place at the vicinity of the pathology (i.e., spatial resolution) can potentially give a better understanding of cause-and-effect relationships during disease progression.

This webcast will describe how Janssen Neuroscience researchers’ testing of a novel, highly sensitive imaging-based in situ transcriptomics technology – Molecular Cartography – detected and quantified the expression of 100 genes in an AD mouse model (APP/PS1). The data demonstrated high sensitivity and specificity of the technology using wild-type mouse cortex as a case study.

The speakers will present a quantitative analysis of changes in 100 genes associated with the following signaling pathways: disease-associated-microglia (DAM), inflammasome, WNT-signaling, and the complement, as a function of distance from Aβ plaques showing the power of spatial transcriptomics as a novel technological advance to study cellular changes in neurodegenerative brain disorders such as Alzheimer’s disease.

You will learn:

  • How to perform highly multiplexed and sensitive spatial transcriptomics
  • If the technique correlates with other transcriptomics data (ISH, ssPCR)?
  • About a method which is as sensitive as other techniques (ISH, PCR)?

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