SFN 2022 Poster: True multiomic in situ single-cell imaging revealed massive pathological changes in Alzheimer’s disease brain

Bin Wang, Yijia Sun, Renchao Chen, Timothy Wiggin, Nicolas Fernandez, Yuan Cai, Yi Sun, George Emanuel, Jiang He

Our understanding of molecular biology and pathology has been greatly facilitated by recent advances in multiple sequencing technologies, coupled with computational analysis, to detect and count proteins and transcripts. However, these tools lack spatial resolution and are unable to map gene expression and cell-cell interaction in a tissue context. Due to the complexity of tissue biology, integrated codetection of proteins and mRNAs from the same cell has the potential to not only reveal the correlation between these two classes of biologically important molecules, but also help understand the mechanisms of gene regulation, at both the transcriptional and translational levels.

Alzheimer’s disease (AD) is currently ranked as the seventh leading cause of death in the United States and is the most common cause of dementia among older adults. Advancements in research have proved fruitful with the recent FDA approved drug Aducanumab (AduhelmTM) from Biogen but further work is needed to drive more effective treatments. The two disease hallmarks: abnormal protein aggregates β-Amyloid plaque (Aβ) and hyperphosphorylated tau Neurofibrillary tangles (NFTs), together with other misfolded proteins during disease progression, cannot be revealed by RNA transcript detection. To address the need for multiomic measurements, Vizgen has recently launched protein codetection products and developed a protocol that allows detection of selected protein targets mapped together with a spatially resolved transcriptomic profile on the MERSCOPE™ Platform.. With downstream multiomic data analysis and MERSCOPE™ Vizualizer software, Aβ/tau proteins and selected gene panel are mapped with respective expression profile to the whole brain section with high resolution. The new MERSCOPE™ protein codetection workflow enables true multiomic analysis and leveraging this comprehensive biological information can drive AD research to ultimately find a cure.