Molecular Characterization of Lewy Body Proteomics Using Laser Capture Microdissection and Mass Spectrometry

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the accumulation of intracellular α-synuclein aggregates known as Lewy bodies. Although Lewy bodies are a defining pathological hallmark of PD, the molecular mechanisms underlying their formation and progression remain incompletely understood. Current molecular analyses often rely on homogenized brain tissue, which may obscure disease-specific molecular changes by combining healthy and diseased cells. Characterizing the molecular profile of Lewy body-containing neurons may provide greater insight into the biological pathways involved in Parkinson’s disease. Human brain tissue sections were stained using immunohistochemistry with antibodies against α-synuclein to identify neurons containing Lewy bodies. Laser capture microdissection (LCM) was then used to isolate these neurons while preserving their spatial context precisely, and the isolated tissue was prepared for downstream protein analysis by mass spectrometry. As protein analysis is ongoing, we expect to identify distinct protein expression patterns associated with Lewy body pathology, including alterations in proteins involved in neurodegeneration, mitochondrial dysfunction, and cellular stress responses. These findings may improve our understanding of Parkinson’s disease and help identify potential biomarkers and therapeutic targets.