Assessment of cortical vulnerability of the anterior cingulate cortex in the behavioral variant of Alzheimer’s disease

Abstract

AbstractBackgroundThe anterior cingulate (ACC) and frontoinsular cortex (FI) are key regions implicated in behavior and social cognition. These regions harbor a novel cortical neuronal group, characterized by expression of the GABA subunit theta (GABRQ) and inclusion of Von Economo Neurons (VENs). This neuronal group is selectively vulnerable in the behavioral variant of frontotemporal dementia (bvFTD), but not in typical Alzheimer’s disease (typAD)(1). Currently, it is unknown whether this neuronal population is affected in the behavioral variant of AD (bvAD) compared to controls and typAD and whether there is a difference in local pathological burden and morphology between bvAD and typAD.MethodHuman post‐mortem tissue of the ACC was used to quantify the GABRQ‐neuronal population and burden and morphology of amyloid beta and tau pathology. We included 10 controls, 8 bvAD donors, and 10 typAD donors. One slide of 10 μm from each donor was used for quantification of Layer 5 GABRQ‐expressing VENs and pyramidal neurons. Layer 5 GABRQ‐negative neurons were counted using Stereoinvestigator software. Burden of pathology was assessed in sequential slides, where diffuse, coarse‐grained, and core amyloid‐beta plaques were quantified. Local tau pathology burden was assessed using ImageJ software. Tissue of the FI will be analyzed in a similar manner.ResultThe total number of GABRQ‐expressing neurons and VENs in the ACC of bvAD donors is similar compared to controls (p=0,22) and typAD (p=0,64)(Figure 1). Furthermore, no significant differences were observed in amyloid‐beta (p=0,38) and tau burden (p=0,09) or presence of different morphological amyloid‐beta plaques in the ACC. Results of FI analysis will be ready at AAIC 2020.ConclusionOur data suggest that the bvAD phenotype cannot be explained by ACC vulnerability to AD pathology. Future analysis of the selective vulnerability of the FI may elucidate whether GABRQ‐expressing neurons are disproportionally affected in bvAD.