Characterization of the Monoamine Oxidase-B (MAO-B) Expression in Postmortem Normal and Alzheimer’s Disease Brains
Methasit Jaisa-aad1, Theresa Connors1, Bradley Hyman1, Alberto Serrano-Pozo1
1Neurology, Massachusetts General Hospital
Objective:
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 MAOB rs1799836 SNP genotype on MAO-B immunoreactivity and all these other measures.
Background:
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 MAOB rs1799836 SNP genotype, which may affect MAO-B enzymatic activity—is lacking.
Design/Methods:
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. MAOB rs1799836 SNP was genotyped in cerebellar DNA via Taqman assay.
Results:
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 MAOB rs1799836 SNP genotype does not affect MAO-B immunoreactivity, AD neuropathological changes, or reactive glia.
Conclusions:
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 MAOB 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.