Disease-in-a-dish studies open a window to a new level of detail in dementia

I started university at the time when induced pluripotent stem cells (iPSCs) – a type of stem cell derived from human skin or blood samples – were first used more regularly in laboratories. Before that, researchers like me would either be working with animal models or non-specific human cell lines. iPSCs offer us an opportunity to conduct experiments on cells that have exactly the same genetic makeup as their donors.

Cohort-derived iPSCs are very useful because we can investigate samples from many people with a range of disease manifestations – and this is what I’m working with now. It’s really exciting.
- Bryan Ng, postdoctoral researcher

Disease in a dish

Rodents like mice and rats do not naturally develop Alzheimer’s disease. Since iPSCs are derived from adult human cells, we are able to take advantage of the human biological and genetic contexts in our studies. Blood samples from Deep and Frequent Phenotyping (DFP) cohort pilot study have allowed us to develop human brain cells – neurons or glial cells – in a dish. Some of the cells are developed from healthy individuals and others from patients in the early clinical stage of Alzheimer’s disease (‘preclinical Alzheimer’s disease as defined by their cognitive status).

This is an amazing resource to work with because it is a relevant cell type and patient-specific. Now, when we conduct our molecular, genetic and protein analyses, we can experiment on the brain cells derived from the patient blood cells. We can then gain more insights into the disease by comparing those with brain cells from healthy individuals in terms of laboratory measurements and clinical assessments.

Correlating cell changes with patient responses

At the moment I’m working on a study with cells derived from the DFP cohort pilot study. These people have had a whole range of different clinical tests, so we have access to fine measurements of their cognitive abilities, and lots of data on brain imaging for example. Here, in the lab I’m working in, we’re studying the brain cells derived from these generous donors. We want to ask if what happens in the clinics is reflected by their respective cells in a dish: disease progression, protein deposition and neuronal connections among others. Thanks to these cells, and the long-term clinical records associated with them, we’re able to study the disease at great detail now, and that should give us all cause to be optimistic.