Negative Correlation of Corpora Amylacea with pTau in the Hippocampus of People with AD

Abstract

AbstractBackgroundRecent studies suggest corpora amylacea (CA) activity may be involved in modulating AD pathology. Normally, CA function in the clearance of brain waste products by amassing cellular debris and extruding it into the cerebrospinal fluid. Disruption of this process may play a role in AD pathogenesis, and its effect might be influenced by degree of tau pathology and genetic risk. In this study, we determined if the abundance of CA was correlated with paired helical filament tau pathology in the CA1 region of the hippocampus in AD postmortem tissue samples. Tau pathology was assessed using both total pTau and total NFTs. Additionally, we investigated whether that correlation was influenced by APOE genotype.MethodPostmortem brain hippocampal tissue sections from 11 brain donors with pre‐mortem cognitive impairment and neuropathologically confirmed AD were double‐stained with Periodic‐acid Schiff (PAS) stain to identify CA and AT8 antibody to identify hyperphosphorylated Tau protein (pTau). Using the Motic slide scanner, stained sections were digitized at 40x. QuPath 0.3.2 was used to extract the CA1 hippocampal region and export to ImageJ for analysis. ImageJ 1.8 color thresholding was used to quantify the number and area of CA and pTau. Neurofibrillary tangle (NFT) pathology was classified by pTau aggregations larger than 150μm2. The percent area occupied (%AO) was calculated by dividing the sum of all positively stained objects by the area of the image, then multiplying by 100. Pearson correlations between CA %AO, pTau %AO, and NFT %AO were calculated in Python 3.7.ResultWhile not statistically significant, we found negative correlations of CA %AO with pTau %AO (‐0.14), and NFT %AO (‐0.28) in the CA1 of the hippocampus. These correlations (‐0.68 and ‐0.54 respectively) were stronger in the 4 individuals who did not carry the AD risk‐increasing APOE‐4 allele.ConclusionThese results suggest that as CA decline, pTau accumulates, which is consistent with prior studies that described a decline in CA from intermediate to advanced Braak Stages (III‐VI) in the dentate gyrus. These changes are consistent with our