Cell studies of Alzheimer's disease progression
Researchers are using samples from the Deep and Frequent phenotyping study pilot
to prepare 'induced pluripotent stem cells' for investigating some of
the earliest changes in Alzheimer's disease.
Induced pluripotent stem cells in Alzheimer's research
Induced pluripotent stem cells (iPSC) are a special type of cell that is proving to be a crucial element in the fight to find the first life-changing treatment for dementia. Unlike embryonic stem cells, they are derived from a sample of blood or skin from adults, but just like an embryonic stem cell they have the capacity to be grown - or 'differentiated' into any other type of human cell. DPUK researchers are using them to study living human brain cells safely outside the body. The techniques they are pioneering are game-changing for dementia research.
A world first for dementia research
The DPUK scientists are making comparisons between patient-derived iPSC brain cells and the known clinical symptoms from these same individuals. This is the largest single dementia stem cells study to date - and the Oxford team who are pioneering the techniques believe that they may be one of few labs in the world taking this approach in Alzheimer's research. Their innovative study is possible thanks to the close collaboration between cohort scientists and those running experimental studies of disease. The scientists are still in the final test stage for the experiments and the researchers are extremely optimistic about the potential of the approach.
I'm really excited because in this study we'll be developing patient-specific Alzheimer's disease modelling for the first time. We're extremely privileged to have a wealth of well-traced clinical test data to work with. This makes a huge difference and significantly improves the interpretation of our lab results.
- Bryan Ng, researcher in the Wade-Martins Lab, University of Oxford
Complex work offers insight into complex disease processes
The researchers are attempting to model human Alzheimer's disease in a dish. First, they used blood cells from volunteers from the Deep and Frequent Phenotyping (DFP) study and turned those cells into pluripotent stem cells using a Nobel prize-winning technique called 'reprogramming'. Pluripotent stem cells are capable of becoming almost any cell type in the body, for example heart, liver or brain cells. The DPUK team are guiding these induced pluripotent cells with a carefully designed protocol so that after 80 days, they become brain cells. Now they have the brain cells, they will conduct experiments to better understand the progress of the disease.
Every patient diagnosed with Alzheimer's disease has a slightly different trajectory of developing symptoms. It's thanks in part to the well-coordinated cohort studies like DFP that laboratory-based researchers like Bryan will be able to learn which biological processes are causing dementia to take hold.
For a more recent update on Bryan's work, read his blog on progress in the dementia stem cells study.
Find out more about the Wade-Martins lab at the University of Oxford.
The research in brief
- Researchers have developed 'induced pluripotent stem cells' from the Deep and Fequent Phenotyping (DFP) study pilot cohort to produce patient-derived neurons.
- Researchers are testing the effects of different stressors on the human neurons to learn more about their behaviour.
- Researchers in three separate labs in the Stem Cell Network are now preparing coordinated experiments in which they will compare cellular features with the clinical symptoms recorded in the cohort data.
Latest publications from DPUK
Prediction of Alzheimer's disease biomarker status defined by the ‘ATN Framework’ among cognitively healthy individuals: Results from the EPAD longitudinal cohort study
CALVIN C. et al, (2020), Alzheimer's Research and Therapy
DPUK's support for this study
Bryan works on the DPUK funded experimental medicine study - 'Integrating clinical and cellular features of dementia'. He works with cohort cell samples that were derived from the pilot study of the Deep and Frequent Phenotyping study and which were subsequently developed DPUK-funded stem cell processing technology.in three labs within DPUK's Stem Cell Network. He works with DPUK-funded stem cell processing technology.