If you use the code in this repository for a publication, please cite the following publication:
Valdes, P., Henry, K.W., Fitzgerald, M.Q., Muralidharan K., Caldwell A.B., Ramachandran S., Goldstein L.S.B., Mobley W.C., Galasko D.R., and Subramaniam S. Limitations of the human iPSC-derived neuron model for early-onset Alzheimer’s disease. Mol Brain 16, 75 (2023). https://doi.org/10.1186/s13041-023-01063-5
Non-familial Alzheimer’s disease (AD) occurring before 65 years of age is commonly referred to as early-onset Alzheimer’s disease (EOAD) and constitutes ~5-6% of all Alzheimer’s disease (AD) cases. While EOAD exhibits the same clinicopathological changes such as amyloid plaques, neurofibrillary tangles (NFTs), brain atrophy, and cognitive decline as observed in the more prevalent late-onset AD (LOAD), EOAD patients tend to have more severe cognitive deficits, including visuospatial, language, and executive dysfunction. Patient-derived induced pluripotent stem cells (iPSCs) have been used to model and study penetrative, familial AD (FAD) mutations in APP, PSEN1, and PSEN2, but have been seldom used for sporadic forms of AD that display more heterogeneous disease mechanisms. In this study, we sought to characterize iPSC-derived neurons from EOAD patients via RNA-sequencing. A modest difference in expression profiles between EOAD patients and non-demented control (NDC) subjects resulted in a limited number of differentially expressed genes (DEGs). Based on this analysis, we provide evidence that iPSC-derived neuron model systems, likely due to the loss of EOAD-associated epigenetic signatures owing to iPSC reprogramming, may not be ideal models for studying sporadic AD.
R and shell scripts with user documentation used for analysis of the Valdes et al. 2023 EOAD RNA-seq Manuscript.
The sequencing data for this project is available at
