Cross‐species evidence of differential expression of S100A6 and SLC11A1 in the hippocampus of Alzheimer’s disease patients and mouse models

Background The evaluation of similarities and differences between mouse models human Alzheimer’s disease (AD) provides invaluable insights on pathophysiology. We compared hippocampal transcriptomic profiles late-onset AD (LOAD) early-onset (EOAD) individuals with three (hAβ-KI, APP/PS1 5xFAD) in an exploratory analysis. Afterwards, we validated the intersection genes consistently altered all groups using tissue from mice, EOAD LOAD patients. Methods Five publicly available AD/cognitively unimpaired (CU) were collected GEO (https://www.ncbi.nlm.nih.gov/geo/), merged submitted to differential expression analysis (DEA) R. model RNAseq data two datasets (GSE149661 GSE145907) also collected. Finally, 5xFAD hAβ-KI obtained AMP-AD Knowledge Portal (https://www.synapse.org/) synapser synapserutils packages. All animal DEA. Validation selected was performed by qRT-PCR. Target mRNA levels normalized β-actin as a housekeeper gene. results expressed relative wild-type (WT) animals or CU controls 2−ΔΔCt method. Results DEA identified 1164, 3261 1782 differentially (DEGs) for comparisons hAβ-KI, mutants versus WT controls, respectively. APP/PS1, mice exhibited more DEGs common than Interestingly, presented However, showed significantly higher APP/PS1. Additionally, S100A6, C1QB, SST, CD14, CD33, SLC11A1 KCNK1 both well evaluated. qRT-PCR these EOAD, revealed S100A6 pathology model. Conclusion Animal seek better simulate pathology, making their molecular overlap greatly important. calcium-binding protein modulating several biological activities, SLC11A1, metal transporter associated inflammatory processes, our transcriptomics analyses experimental validation, them promising targets further investigation.