Reduction of neurogranin protein correlates with increases of inflammasome proteins in post mortem cases of intermediate Alzheimer’s disease

BACKGROUND: Neurogranin (Ng) is considered a biomarker for synaptic dysfunction in Alzheimer's disease (AD). In contrast, the inflammasome complex has been shown to exacerbate AD pathology. METHOD: We investigated the protein expression, morphological differences of Ng and correlated Ng to hyperphosphorylated tau in the postmortem brains of 17 AD cases and 17 age and sex-matched controls. In addition, we correlated the Ng expression with two different epitopes of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). RESULT: We show a reduction of Ng immunopositive neurons and morphological differences in AD compared to controls. Ng immunostaining was negatively correlated with neurofibrillary tangles, humanized anti-ASC (IC100) positive neurons and anti- ASC positive microglia, in AD. CONCLUSION: The finding of a negative correlation between Ng and ASC speck protein expression in postmortem brains of AD suggests that the activation of inflammasome/ASC speck pathway may play an important role in synaptic degeneration in AD.