Generation and characterisation of a panel of human iPSC-derived neurons and microglia carrying early and late onset relevant mutations for Alzheimer’s disease

Alzheimer’s disease (AD) is the most common type of dementia, contributing 60-70% of cases, and affecting more than 24 million people worldwide. There are no disease-modifying treatments available and existing drugs only treat the symptoms and not the root cause of the disease. Development of therapies for AD is hampered because less than 10% of findings derived from preclinical animal models can be translated to humans. Patient-derived induced pluripotent stem cells (iPSCs) enable generation of in vitro models that can recapitulate human disease phenotypes.
 
Key learnings from the poster:

• ioGlutamatergic Neurons, ioGABAergic Neurons and ioMicroglia have been precision reprogrammed from human iPSCs into consistent, mature, functional neurons or microglia showing a high level of transcriptomic similarity between lots.
• A panel of disease model cells carrying Alzheimer’s disease-relevant mutations within the APP, PSEN1, APOE & TREM2 genes were generated from the wild type iPSC lines using CRISPR/Cas9 gene engineering.
• The disease model cells showed similar protein expression of key neuronal or microglia markers to the genetically matched wild-type control, ensuring biological comparability of the disease models.
• The ioMicroglia APOE 4/4 and TREM2 R47H Het disease models also show reduced phagocytic activity compared to the genetically matched wild-type control.