Cell-specific protein expression in Alzheimer's disease prefrontal cortex.

INTRODUCTION: Analyzing the proteomes of different brain cell types is fundamental for understanding the pathophysiology of Alzheimer's disease (AD). However, spatial analysis of these diverse and limited cell populations poses significant challenges. METHODS: The GeoMx Digital Spatial Profiler (DSP) platform was used to analyze protein level in the prefrontal cortex of AD and non-AD brains. The platform interrogated 76 proteins and used immunofluorescence to distinguish between three cell types. RESULTS: Neprilysin (NEP), which promotes amyloid beta degradation, was significantly higher in AD neurons and microglia. Lysosome-associated membrane protein 2A (LAMP2A) level was higher in neurons of individuals with AD compared to a control group. In addition, markers of neuroinflammation, such as CD11c, CD11b, and CD163, were also elevated in AD neurons. DISCUSSION: Our findings indicate the DSP platform effectively facilitates cell-specific snapshots of the AD brain proteome. HIGHLIGHTS: The expression of 76 proteins was studied in neurons, astrocytes, and microglia. We identified 18 differentially expressed proteins in AD neurons. Neprilysin was upregulated in neurons and microglia.