| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Cells, Vol 11, Iss 20, p 3258 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2073-4409 |
| DOI: |
10.3390/cells11203258 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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