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

iScience (Jan 2024)

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

Journal volume & issue: Vol. 27, no. 1
p. 108671

Abstract

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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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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