Cross-species comparative hippocampal transcriptomics in Alzheimer's disease

Marco Antônio De Bastiani; Bruna Bellaver; Giovanna Carello‐Collar; Maria Zimmermann; Peter Kunach; Ricardo A. S. Lima‐Filho; Stefânia Forner; Alessandra Cadete Martini; Tharick Ali Pascoal; Mychael V. Lourenco; Pedro Rosa‐Neto; Eduardo Rigon Zimmer

doi:10.1016/j.isci.2023.108671

NeuroscienceiScienceDec 7, 2023

Peer-reviewed journal article

Cross-species comparative hippocampal transcriptomics in Alzheimer's disease

Marco Antônio De Bastiani iD, Bruna Bellaver iD, Giovanna Carello‐Collar iD, Maria Zimmermann iD, Peter Kunach iD, Ricardo A. S. Lima‐Filho iD, Stefânia Forner iD, Alessandra Cadete Martini iD, Tharick Ali Pascoal iD, Mychael V. Lourenco iD, Pedro Rosa‐Neto iD, Eduardo Rigon Zimmer iD

Abstract

Alzheimers disease (AD) is a multifactorial pathology, with most cases having a sporadic origin. Recently, knock-in (KI) models have been developed with the promise of resembling better sporadic human AD, such as the novel hA{beta}-KI mouse. Here, we compared hippocampal publicly available transcriptomic profiles of transgenic (5xFAD and APP/PS1) and KI (hA{beta}-KI) mouse models with early- (EOAD) and late- (LOAD) onset AD patients. Experimental validation of consistently dysregulated genes revealed four altered in mice (SLC11A1, S100A6, CD14, CD33, C1QB) and three in humans (S100A6, SLC11A1, KCNK). Additionally, the three mouse models presented more Gene Ontology biological processes terms and enriched signaling pathways in common with LOAD than with EOAD individuals. Finally, we identified 17 transcription factors potentially acting as master regulators of AD. Our cross-species analyses revealed that the three mouse models presented a remarkable similarity to LOAD, with the hA{beta}-KI being the more specific one.

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