An Alzheimer’s Disease Patient-Derived Olfactory Stem Cell Model Identifies Gene Expression Changes Associated with Cognition
Laura M. Rantanen,
Maina Bitar,
Riikka Lampinen,
Romal Stewart,
Hazel Quek,
Lotta E. Oikari,
Carla Cunί-Lόpez,
Ratneswary Sutharsan,
Gayathri Thillaiyampalam,
Jamila Iqbal,
Daniel Russell,
Elina Penttilä,
Heikki Löppönen,
Juha-Matti Lehtola,
Toni Saari,
Sanna Hannonen,
Anne M. Koivisto,
Larisa M. Haupt,
Alan Mackay-Sim,
Alexandre S. Cristino,
Katja M. Kanninen,
Anthony R. White
Affiliations
Laura M. Rantanen
Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia
Maina Bitar
Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia
Riikka Lampinen
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, Finland
Romal Stewart
Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia
Hazel Quek
Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia
Lotta E. Oikari
Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia
Carla Cunί-Lόpez
Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia
Ratneswary Sutharsan
Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia
Gayathri Thillaiyampalam
Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia
Jamila Iqbal
Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia
Daniel Russell
Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia
Elina Penttilä
Department of Otorhinolaryngology, University of Eastern Finland, Kuopio University Hospital, 70210 Kuopio, Finland
Heikki Löppönen
Department of Otorhinolaryngology, University of Eastern Finland, Kuopio University Hospital, 70210 Kuopio, Finland
Juha-Matti Lehtola
Brain Research Unit, Department of Neurology, School of Medicine, University of Eastern Finland, 70210 Kuopio, Finland
Toni Saari
Brain Research Unit, Department of Neurology, School of Medicine, University of Eastern Finland, 70210 Kuopio, Finland
Sanna Hannonen
Brain Research Unit, Department of Neurology, School of Medicine, University of Eastern Finland, 70210 Kuopio, Finland
Anne M. Koivisto
Brain Research Unit, Department of Neurology, School of Medicine, University of Eastern Finland, 70210 Kuopio, Finland
Larisa M. Haupt
Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
Alan Mackay-Sim
Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia
Alexandre S. Cristino
Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia
Katja M. Kanninen
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, Finland
Anthony R. White
Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia
An early symptom of Alzheimer’s disease (AD) is an impaired sense of smell, for which the molecular basis remains elusive. Here, we generated human olfactory neurosphere-derived (ONS) cells from people with AD and mild cognitive impairment (MCI), and performed global RNA sequencing to determine gene expression changes. ONS cells expressed markers of neuroglial differentiation, providing a unique cellular model to explore changes of early AD-associated pathways. Our transcriptomics data from ONS cells revealed differentially expressed genes (DEGs) associated with cognitive processes in AD cells compared to MCI, or matched healthy controls (HC). A-Kinase Anchoring Protein 6 (AKAP6) was the most significantly altered gene in AD compared to both MCI and HC, and has been linked to cognitive function. The greatest change in gene expression of all DEGs occurred between AD and MCI. Gene pathway analysis revealed defects in multiple cellular processes with aging, intellectual deficiency and alternative splicing being the most significantly dysregulated in AD ONS cells. Our results demonstrate that ONS cells can provide a cellular model for AD that recapitulates disease-associated differences. We have revealed potential novel genes, including AKAP6 that may have a role in AD, particularly MCI to AD transition, and should be further examined.
