Elevated Monoamine Oxidase-A in Anterior Cingulate of Post-Mortem Human Parkinson’s Disease: A Potential Surrogate Biomarker for Lewy Bodies?

Abstract

Lewy bodies (LB) play a neuropathological role in Parkinson's disease (PD). Our goal was to evaluate LB using anti-ubiquitin immunohistochemistry (UIHC) and find correlations with monoamine oxidase-A (MAO-A) using imaging agent, [18F]FAZIN3. Human post-mortem anterior cingulate (AC) and corpus callosum (CC) from control subjects (CN), n = 6; age 81-90 LB = 0 and PD, n = 6, age 77-89, LB = III-IV were sectioned (10 μm slices). Brain slices were immunostained with anti-ubiquitin for LB (UIHC) and analyzed using QuPath for percent anti-ubiquitin per unit area (μm2). Adjacent brain slices were incubated with [18F]FAZIN3 and cortical layers I-III, IV-VI and CC (white matter) regions were quantified for the binding of [18F]FAZIN3. UIHC was correlated with [18F]FAZIN3 binding. All PD brains were positively UIHC stained and confirmed presence of LB. Outer cortical layers (I-III) of PD AC had 21% UIHC while inner layers (IV-VI) had >75% UIHC. In the CN brains LB were absent (<1% UIHC). Increased [18F]FAZIN3 binding to MAO-A in AC was observed in all PD subjects. [18F]FAZIN3 ratio in PD was AC/CC = 3.57 while in CN subjects it was AC/CC = 2.24. Increases in UIHC μm2 correlated with [18F]FAZIN3 binding to MAO-A in DLU/mm2. Increased [18F]FAZIN3 binding to MAO-A in PD is a potential novel "hot spot" PET imaging approach.