Spatial Transcriptomics Reveals Genes Associated with Dysregulated Mitochondrial Functions and Stress Signaling in Alzheimer Disease
José Fernández Navarro,
Deborah L. Croteau,
Aleksandra Jurek,
Zaneta Andrusivova,
Beimeng Yang,
Yue Wang,
Benjamin Ogedegbe,
Tahira Riaz,
Mari Støen,
Claus Desler,
Lene Juel Rasmussen,
Tone Tønjum,
Marie-Christine Galas,
Joakim Lundeberg,
Vilhelm A. Bohr
Affiliations
José Fernández Navarro
Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, 17165 Stockholm, Sweden
Deborah L. Croteau
Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD 21224, USA
Aleksandra Jurek
Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, 17165 Stockholm, Sweden
Zaneta Andrusivova
Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, 17165 Stockholm, Sweden
Beimeng Yang
Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD 21224, USA
Yue Wang
Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD 21224, USA
Benjamin Ogedegbe
Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD 21224, USA
Tahira Riaz
Unit for Genome Dynamics, Department of Microbiology, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway
Mari Støen
Unit for Genome Dynamics, Department of Microbiology, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway
Claus Desler
Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
Lene Juel Rasmussen
Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
Tone Tønjum
Unit for Genome Dynamics, Department of Microbiology, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway
Marie-Christine Galas
University of Lille, Inserm, CHU Lille, UMR-S 1172 - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, 59000 Lille, France
Joakim Lundeberg
Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, 17165 Stockholm, Sweden
Vilhelm A. Bohr
Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD 21224, USA; Unit for Genome Dynamics, Department of Microbiology, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway; Corresponding author
Summary: Alzheimer disease (AD) is a devastating neurological disease associated with progressive loss of mental skills and cognitive and physical functions whose etiology is not completely understood. Here, our goal was to simultaneously uncover novel and known molecular targets in the structured layers of the hippocampus and olfactory bulbs that may contribute to early hippocampal synaptic deficits and olfactory dysfunction in AD mice. Spatially resolved transcriptomics was used to identify high-confidence genes that were differentially regulated in AD mice relative to controls. A diverse set of genes that modulate stress responses and transcription were predominant in both hippocampi and olfactory bulbs. Notably, we identify Bok, implicated in mitochondrial physiology and cell death, as a spatially downregulated gene in the hippocampus of mouse and human AD brains. In summary, we provide a rich resource of spatially differentially expressed genes, which may contribute to understanding AD pathology.
