Cross-species comparative hippocampal transcriptomics in Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial pathology, with most cases having a sporadic origin. Recently, knock-in (KI) mouse models, such as the novel humanized amyloid-β (hAβ)-KI, have been developed to better resemble sporadic human AD.
Methods: Here, we compared hippocampal publicly available transcriptomic profiles of transgenic (5xFAD and APP/PS1) and KI (hAβ-KI) mouse models with early- (EOAD) and late- (LOAD) onset AD patients.
Results: The three mouse models presented more Gene Ontology biological processes terms and enriched signaling pathways in common with LOAD than with EOAD individuals. Experimental validation of consistently dysregulated genes revealed five altered in mice (SLC11A1, S100A6, CD14, CD33, and C1QB) and three in humans (S100A6, SLC11A1, and KCNK). Finally, we identified 17 transcription factors potentially acting as master regulators of AD.
Conclusion: Our cross-species analyses revealed that the three mouse models presented a remarkable similarity to LOAD, with the hAβ-KI being the more specific one.
Competing Interests: E.R.Z. is a member of the Scientific Advisory Board of Nintx, Co-founder and member of the Scientific Advisory Board of MASIMA and served in the Scientific Advisory Board of Novo Nordisk. M.A.B. is the CFO of MASIMA.
(© 2023 The Authors.)