Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Multifactorial omics platforms for studying Alzheimer's disease olfactory cells (#802)

Laura Rantanen 1 2 , Anthony White 1 , Larisa Haupt 2 , Katja Kanninen 3
  1. QIMR Berghofer Medical Research Institute, Brisbane City, QDL, Australia
  2. Queensland University of Technology, Brisbane City, QDL, Australia
  3. University of Eastern Finland, Kuopio, Finland

Neurodegenerative diseases, such as Alzheimer’s disease (AD) cause a significant burden to health and socio-economic sectors worldwide. Previous attempts to generate amyloid-targeting strategies have failed to translate to clinical outcomes. Hence, new approaches targeting the underlying molecular pathways of AD are urgently required. An impaired sense of smell is one of the earliest symptoms and a significant predictor of conversion to AD from mild cognitive impairment (MCI). The olfactory mucosa, the organ of smell in the nose, contains a unique niche of stem cells that are capable of replenishing nasal receptor neurons and supporting cells in the nose throughout adult life. These cells can be collected from patients with relative ease and can easily be expanded in the laboratory to generate human olfactory neurosphere-derived cells (hONS). Patient-derived olfactory cells have demonstrated disease-associated differences in several neuronal diseases, such as Parkinson’s disease, schizophrenia, familial dysautonomia and ataxia telangiectasia. The main objective of this study is to identify significant differences in gene, protein, and lipid metabolism between control and AD patient-derived olfactory cells. This will also be extended to people with MCI, who may have early changes of AD. Analyses consist of global RNA sequencing, and proteomic screening of cells using subcellular fractionation and liquid chromatography in combination with tandem mass spectrometry (LC-MS/MS). In addition, we will also carry out assays to determine changes in neuroinflammation and mitochondrial function between control, MCI and AD-patient-derived olfactory cells. This study will help elucidate the involvement of the olfactory system in pathogenesis of AD and provide new insights into Alzheimer’s disease pathways, biomarkers and therapeutic targets.