Quantification of the neuropathology of alcohol use disorder using tissue microarrays

Alcohol use disorder (AUD) is characterized by an inability to stop consuming alcohol. Neuroimaging studies of patients with AUD show mild grey and white matter atrophy, while pathological studies suggest that atrophy is restricted to the white matter. The effects on individual brain cells are largely unknown. Mild neuronal loss has been described in the prefrontal cortex but this has not been consistent. Studies quantifying oligodendrocytes, astrocytes, and microglia are rare. These knowledge gaps impede therapeutic advancements. Here, we piloted the use of tissue microarrays, immunohistochemistry, and automated image analysis to systematically quantify cell profiles in human postmortem tissue. We sampled 173 grey and white matter cores across 5 cerebral regions from 4 male AUD cases and 4 age-matched controls. We found no obvious differences in the regional profiles of neurons, astrocytes, oligodendrocytes, or microglia. However, mean microglial densities across all regions were higher in AUD (P=.0024). There were visual signs of reactive astrocytosis in AUD cases but mean cell body sizes were unchanged. Our findings suggest that alcohol-related brain damage is not due to a loss of any of major cell classes. Larger studies focusing on subtype-specific markers and advanced image analysis tools are required.