Human Brain Cell Type Classification Using Spatial Proteomics

Alzheimer’s Disease (AD) is the most common form of dementia affecting the population over the age of 65. AD is characterized clinically by increasing difficulty with memory and language, resulting in a loss of independence. This is due to the presence of two characteristic protein aggregates in the brain: extracellular amyloid plaques and intracellular neurofibrillary tangles (NFTs). Utilizing multiplexed immunofluorescence and dimensional reduction analysis the types of cells present in the hippocampus, the region of the brain most affected by AD, can be explored. Understanding the kinds of cell subtypes present, the mechanism behind how AD develops can be explored. Multiplexed IF was performed on human hippocampus FFPE tissues to detect a total of 37 proteins. Dimensional reduction analysis was performed to identify the four major cell types in the brain: neurons, oligodendrocytes, astrocytes, and microglia. After identifying each cell type, further dimensional reduction analysis was performed within each cell type to identify cell subtypes. A total of 21 neuron, 41 oligodendrocyte, 20 astrocyte, and 22 microglia subtypes were identified. The location of cell subtypes in each region of the hippocampal formation was found to match previous reports, further validating the findings of this project.