Exploring the Brain with Spatial Biology

Spatial biology—analyzing the levels and locations of gene or protein expression within tissues—is boosting our understanding of many tissue types, but its application to the brain is especially revealing. With myriad cell types and innumerable cell-cell interactions, the brain’s mysteries are slowly unraveling as researchers apply spatial biology’s facility for tissue mapping and cell atlasing. The result is new insights into disease pathologies, and the mechanisms of neurodegenerative changes that occur in the brain. Here’s a look at how researchers are using spatial biology to study Alzheimer’s disease.

Studying AD with single-cell gene expression

Gene expression studies can help us understand the physiological roles of distinct cell types, and pinpoint potential disease mechanisms. Vizgen’s MERSCOPE® platform allows researchers to study single-cell gene expression in situ. It uses high-resolution spatial imaging along with spatial transcriptomics as measured by MERFISH (multiplexed error-robust fluorescence in situ hybridization) labeling and detection.

Researchers at the Allen Institute for Brain Science used MERSCOPE and single cell analysis to create a comprehensive, multimodal cell atlas of AD in the human brain. “They mapped the spatial distribution of different cell types in the human brain at different stages of AD, and characterized the proportional changes of specific cell supertypes as a function of disease severity,” says Jiang He, Scientific Co-Founder and Senior Director of Scientific Affairs at Vizgen. “Intriguingly, they found an early reduction of SST inhibitory neuronal subtypes, and a late decrease of supragranular IT excitatory neurons and Plvb+ inhibitory neurons, during disease progression.”

Brain tissue presents unique challenges in spatial biology, such as the complicating presence of lipofuscin, brownish pigment-containing granules often present in aging brains that can interfere with imaging by causing background autofluorescence. “To [help with this], Vizgen developed a MERSCOPE Photobleacher, and implemented a tissue clearing step during sample prep to reduce the background, enabling researchers to image human brain samples at different ages or disease stages.”

Spatial biology technologies like MERSCOPE continue to fuel cell atlasing efforts to create reference maps of the brain—and scientists will continue to rely on these maps to integrate multi-omics data into an understanding of brain function. “For example, combining multiplexed protein imaging with MERSCOPE imaging, researchers will be able to visualize plaques in AD patients’ brains, and characterize the cellular composition and states around the plaques,” he says. As spatial biology methods continue to advance, the further unlocking of brain mysteries will continue to intrigue us.