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,
Stefania Forner,
Alessandra Cadete Martini,
Tharick A. Pascoal,
Mychael V. Lourenco,
Pedro Rosa-Neto,
Eduardo R. Zimmer
Affiliations
Marco Antônio De Bastiani
Graduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, Institute of Health Basic Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, State of Rio Grande do Sul 90035-003, Brazil
Bruna Bellaver
Department of Psychiatry, School of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Giovanna Carello-Collar
Graduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, Institute of Health Basic Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, State of Rio Grande do Sul 90035-003, Brazil
Maria Zimmermann
Department of Neurology and Neurosurgery, Montréal Neurological Institute, McGill University, Montréal, Québec H3A 1A1, Canada; Translational Neuroimaging Laboratory, McGill University, Montréal, Québec H4H 1R3, Canada
Peter Kunach
Department of Neurology and Neurosurgery, Montréal Neurological Institute, McGill University, Montréal, Québec H3A 1A1, Canada; Translational Neuroimaging Laboratory, McGill University, Montréal, Québec H4H 1R3, Canada; Douglas Hospital Research Centre, Montreal, Québec H4H 1R3, Canada
Ricardo A.S. Lima-Filho
Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, State of Rio de Janeiro 21941-902, Brazil
Stefania Forner
Institute for Memory Impairments and Neurological Disorders (UCI MIND), University of California, Irvine, Irvine, CA 92697, USA
Alessandra Cadete Martini
Department of Pathology & Laboratory Medicine, University of California, Irvine, Irvine, CA 92697, USA
Tharick A. Pascoal
Department of Psychiatry, School of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Department of Neurology, School of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Mychael V. Lourenco
Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, State of Rio de Janeiro 21941-902, Brazil
Pedro Rosa-Neto
Department of Neurology and Neurosurgery, Montréal Neurological Institute, McGill University, Montréal, Québec H3A 1A1, Canada; Translational Neuroimaging Laboratory, McGill University, Montréal, Québec H4H 1R3, Canada; Douglas Hospital Research Centre, Montreal, Québec H4H 1R3, Canada
Eduardo R. Zimmer
Graduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, Institute of Health Basic Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, State of Rio Grande do Sul 90035-003, Brazil; Department of Pharmacology, ICBS, UFRGS, Porto Alegre, State of Rio Grande do Sul 90035-003, Brazil; Graduate Program in Biological Sciences: Pharmacology and Therapeutics, Department of Pharmacology, ICBS, UFRGS, Porto Alegre, State of Rio Grande do Sul 90035-003, Brazil; Corresponding author
Summary: 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.
