Characterization of the Monoamine Oxidase-B (MAO-B) Expression in Postmortem Normal and Alzheimer’s Disease Brains (S39.006)

Abstract

<h3>Objective:</h3> To characterize MAO-B expression in postmortem human control (CTRL) and Alzheimer’s disease (AD) brains. Specifically, we sought to: (1) Identify the cell type(s) expressing MAO-B; (2) Compare MAO-B immunoreactivity in CTRL vs. AD brains; (3) Correlate MAO-B levels with local measures of AD neuropathological changes, cortical thickness, and reactive glia; (4) Evaluate the impact of the <i>MAOB</i> rs1799836 SNP genotype on MAO-B immunoreactivity and all these other measures. <h3>Background:</h3> MAO-B has been proposed as a novel PET imaging biomarker of AD-associated reactive astrogliosis. However, a thorough characterization in postmortem CTRL and AD brains—including the impact of the <i>MAOB</i> rs1799836 SNP genotype, which may affect MAO-B enzymatic activity—is lacking. <h3>Design/Methods:</h3> We performed automated MAO-B immunohistochemistry on FFPE sections from multiple brain regions of CTRL and AD brain donors followed by whole-slide scan and quantification of cortical and white matter immunoreactivity using QuPath pixel classifier. <i>MAOB</i> rs1799836 SNP was genotyped in cerebellar DNA via Taqman assay. <h3>Results:</h3> We found that: (1) MAO-B is primarily expressed by cortical and white matter astrocytes; (2) MAO-B is elevated in AD vs. CTRL astrocytes uniformly across the temporal, frontal, and occipital cortex and white matter; (3) cortical MAO-B immunoreactivity correlates positively with the number of GFAP+ reactive astrocytes and CD68+ activated microglia, and negatively with cortical thickness, but not with Aβ plaque load or number of neurofibrillary tangles; (4) the <i>MAOB</i> rs1799836 SNP genotype does not affect MAO-B immunoreactivity, AD neuropathological changes, or reactive glia. <h3>Conclusions:</h3> Astrocytes are the main cellular source of MAO-B in the cerebral cortex. MAO-B levels are significantly increased in the AD cortex and parallel the number of GFAP+ reactive astrocytes. The <i>MAOB</i> rs1799836 SNP genotype does not impact any of these measures. MAO-B is a promising target for the development of PET imaging radiotracers of reactive astrogliosis. <b>Disclosure:</b> Dr. Jaisa-aad has nothing to disclose. Ms. Connors has nothing to disclose. An immediate family member of Dr. Hyman has received personal compensation for serving as an employee of novartis. Dr. Hyman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for dewpoint. Dr. Hyman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for abbvie. Dr. Hyman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arvinas. Dr. Hyman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for avrobio. Dr. Hyman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Hyman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Dept of Justice. Dr. Hyman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cell Signalling. Dr. Hyman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sangamo. Dr. Hyman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for sanofi. Dr. Hyman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for vigil. Dr. Hyman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for voyager. Dr. Hyman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for biogen. Dr. Hyman has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for dept of justice. Dr. Hyman has stock in dewpoint. The institution of Dr. Hyman has received research support from nih. The institution of Dr. Hyman has received research support from JPB. The institution of Dr. Hyman has received research support from Cure Alz Fund. The institution of Dr. Hyman has received research support from Tau consortium. The institution of Dr. Hyman has received research support from abbvie. The institution of Dr. Hyman has received research support from BMS. Dr. Serrano-Pozo has received research support from NIH/NIA. Dr. Serrano-Pozo has received research support from Alzheimer’s Association. Dr. Serrano-Pozo has received research support from The Jack Satter Foundation. Dr. Serrano-Pozo has received research support from The Karen Toffler Charitable Trust. Dr. Serrano-Pozo has received research support from Ionis Pharmaceuticals, Inc. Dr. Serrano-Pozo has received research support from AbbVie, Inc..