An Alzheimer's Disease Patient-Derived Olfactory Stem Cell Model Identifies Gene Expression Changes Associated with...

Area of Science:

• Neuroscience
• Genetics
• Cell Biology

Background:

• An early symptom of Alzheimer's disease (AD) is a diminished sense of smell, but its molecular underpinnings are not well understood.
• Olfactory neurosphere-derived (ONS) cells offer a potential model for studying early AD-related molecular changes.

Purpose of the Study:

• To investigate gene expression differences in olfactory cells from individuals with Alzheimer's disease (AD) and mild cognitive impairment (MCI) compared to healthy controls (HC).
• To identify novel genes and pathways involved in the early stages of AD, particularly the transition from MCI to AD.

Main Methods:

• Generation of human olfactory neurosphere-derived (ONS) cells from individuals with AD, MCI, and HC.
• Global RNA sequencing (transcriptomics) to analyze gene expression profiles.
• Bioinformatic analysis to identify differentially expressed genes (DEGs) and dysregulated pathways.

Main Results:

• ONS cells exhibited neuroglial differentiation markers, validating their use as an AD cellular model.
• Significant differences in gene expression were observed between AD, MCI, and HC ONS cells.
• A-Kinase Anchoring Protein 6 (AKAP6) was the most significantly altered gene in AD ONS cells compared to MCI and HC.
• Dysregulated pathways in AD ONS cells included those related to aging, intellectual deficiency, and alternative splicing.

Conclusions:

• ONS cells provide a viable cellular model for recapitulating AD-associated molecular changes.
• AKAP6 is a potential novel gene implicated in AD pathogenesis, especially during the MCI to AD transition.
• Further research into AKAP6 and identified pathways is warranted to understand early AD mechanisms.