Patient-specific stem cells are key to understanding Alzheimer’s. Researchers can turn stem cells into brain cells, which are not easily accessible from living patients, in the laboratory. One of the major challenges in studying these brain cells has been to model pathological changes characteristic of Alzheimer’s brains in the majority of patients who do not harbour genetic mutations that cause disease.
To tackle this issue, a collaborative study involving researchers from the University of Oxford and the clinical team from the Deep and Frequent Phenotyping cohort of early Alzheimer’s utilised blood samples donated by fourteen Alzheimer’s patients from multiple centres around the UK. The researchers converted the blood cells into stem cells before generating brain cells specific to each individual donor. Researchers then challenged these brain cells with toxic amyloid-beta - a key pathological protein in Alzheimer’s - to cause synapse loss. A loss of synapses – the junctions where brain cell communication takes place - is the strongest correlate for cognitive decline in Alzheimer's.
The team found that the extent of synapse loss varies among individual patient brain cell lines, and crucially, correlates with their clinical symptoms, such as cognitive decline or brain activity, given their varying levels of amyloid-beta burden in the brain.
First author, Dr Bryan Ng from Professor Richard Wade-Martins’ laboratory, said: “We are excited to have found that brain cells generated in the laboratory from individual Alzheimer’s patients reflect their clinical vulnerability to amyloid-beta. This will help us better understand mechanisms of resilience and will help in the search for new therapeutic strategies”.
The full paper ‘Neurons derived from individual early Alzheimer’s disease patients reflect their clinical vulnerability’ is available to read in Brain Communications.
Collaborating University of Oxford departments include DPAG, the Kavli Institute for Nanoscience Discovery, the Nuffield Department of Clinical Neurosciences, and the Department of Psychiatry.