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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.<\/jats:p>","DOI":"10.3390\/cells11203258","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T05:08:02Z","timestamp":1665983282000},"page":"3258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["An Alzheimer\u2019s Disease Patient-Derived Olfactory Stem Cell Model Identifies Gene Expression Changes Associated with Cognition"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7162-1459","authenticated-orcid":false,"given":"Laura M.","family":"Rantanen","sequence":"first","affiliation":[{"name":"Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"},{"name":"Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maina","family":"Bitar","sequence":"additional","affiliation":[{"name":"Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1485-5179","authenticated-orcid":false,"given":"Riikka","family":"Lampinen","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romal","family":"Stewart","sequence":"additional","affiliation":[{"name":"Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5597-5372","authenticated-orcid":false,"given":"Hazel","family":"Quek","sequence":"additional","affiliation":[{"name":"Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotta E.","family":"Oikari","sequence":"additional","affiliation":[{"name":"Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Cun\u03af-L\u03ccpez","sequence":"additional","affiliation":[{"name":"Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratneswary","family":"Sutharsan","sequence":"additional","affiliation":[{"name":"Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayathri","family":"Thillaiyampalam","sequence":"additional","affiliation":[{"name":"Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamila","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4719-4706","authenticated-orcid":false,"given":"Daniel","family":"Russell","sequence":"additional","affiliation":[{"name":"Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elina","family":"Penttil\u00e4","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, University of Eastern Finland, Kuopio University Hospital, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heikki","family":"L\u00f6pp\u00f6nen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, University of Eastern Finland, Kuopio University Hospital, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1018-0186","authenticated-orcid":false,"given":"Juha-Matti","family":"Lehtola","sequence":"additional","affiliation":[{"name":"Brain Research Unit, Department of Neurology, School of Medicine, University of Eastern Finland, 70210 Kuopio, Finland"},{"name":"Department of Neurology, Neuro Centre, Kuopio University Hospital, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni","family":"Saari","sequence":"additional","affiliation":[{"name":"Brain Research Unit, Department of Neurology, School of Medicine, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanna","family":"Hannonen","sequence":"additional","affiliation":[{"name":"Brain Research Unit, Department of Neurology, School of Medicine, University of Eastern Finland, 70210 Kuopio, Finland"},{"name":"Department of Neurology, Neuro Centre, Kuopio University Hospital, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M.","family":"Koivisto","sequence":"additional","affiliation":[{"name":"Brain Research Unit, Department of Neurology, School of Medicine, University of Eastern Finland, 70210 Kuopio, Finland"},{"name":"Department of Neurology, Neuro Centre, Kuopio University Hospital, 70210 Kuopio, Finland"},{"name":"Department of Neurology and Geriatrics, Helsinki University Hospital and Neurosciences, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7735-8110","authenticated-orcid":false,"given":"Larisa M.","family":"Haupt","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology (QUT), Brisbane, QLD 4059, 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Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1802-9891","authenticated-orcid":false,"given":"Anthony R.","family":"White","sequence":"additional","affiliation":[{"name":"Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"},{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, Finland"},{"name":"Faculty of Medicine, University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/ene.13439","article-title":"Alzheimer\u2019s disease","volume":"25","author":"Lane","year":"2018","journal-title":"Eur. J. 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