SFN 2023 Poster-Spatially resolved, single-cell transcriptomic imaging with protein biomarkers in human Alzheimer’s Disease brain samples

Bin Wang, Hao Wang, Yijia Sun, Jiang He


Elucidating the underlying molecular alterations in Alzheimer’s Disease (AD) pathology is essential for understanding disease mechanisms and developing effective therapeutic interventions. In recent years, multiplexed imaging techniques have emerged as powerful tools for comprehensive molecular and cellular profiling at single-cell resolution. In this study, we used the Vizgen® MERSCOPE® Platform, a single-cell, spatially resolved transcriptomic imaging system, to study the spatial distribution of biomarkers and cellular heterogeneity of a normal aging human brain sample and a human AD brain sample by simultaneously imaging up to 6 protein biomarkers and hundreds of RNA species together. Specifically, we employed a representative 6-plex neuronal protein panel comprising cell type markers (GFAP, SMA, MBP), a vascular protein (CD31), and neuropathological markers (mOC23, AT8), in conjunction with a custom 244-plex gene panel*, to explore the intricate molecular and cellular signatures within affected brain regions. We demonstrated that protein co-detection did not negatively impact the detection of RNA transcripts in tissue, and that the simultaneous protein staining revealed distinct morphological and pathological features of the disease. Additionally, in situ profiling of hundreds of RNAs on the same tissue section at single-cell resolution enabled us to map and catalog major cell types. By simultaneously examining markers for neurons, astrocytes, microglia, and other relevant cell populations, we can elucidate the cellular composition and potential alterations in cellular states associated with AD progression. The proposed utilization of spatial multiomic profiling of both protein and RNA offers a comprehensive approach to investigate protein expression patterns, cellular heterogeneity, and cell-cell interaction in AD pathology, highlighting the power of spatial multiomics in understanding complex diseases such as AD. This information will contribute to a deeper understanding of the cellular and molecular mechanisms involved in the disease, potentially identifying novel targets for therapeutic intervention.

*RUO only, not approved for diagnostic or therapeutic purposes.