Researchers at the University of Oxford have been able to show that brain cells created in the laboratory from Alzheimer patients’ blood samples reflect the damage that is seen in the brains of the same patients. These cells showed a loss of synapse function, accurately reflecting the decline in cognitive function seen in the actual brain activity of individual patients. The findings reveal the potential for predicting the disease at an early stage from the blood samples themselves.
Significance of the research
The research is the result of advances in biomarker research, making it possible to identify Alzheimer’s disease even before symptoms emerge by looking at how vulnerable cells from healthy individuals are to amyloid proteins. A better understanding of this preclinical stage of Alzheimer’s increases opportunities both for early intervention and the potential for therapeutic success. In addition, the approach opens the door for checking if a treatment would work on a particular patient by testing it first on cells they have donated.
The researchers at the University of Oxford worked alongside a clinical group studying the Deep and Frequent Phenotyping cohort of early Alzheimer’s patients. They utilised blood samples donated by fourteen Alzheimer’s patients from centres around the UK. The researchers then converted some of their blood cells into stem cells before generating brain cells specific to each individual donor. Stem cells are key to understanding neurological disorders, like Alzheimer’s.
The team believes the presence of toxic amyloid-beta - a key pathological protein in Alzheimer’s – causes synapse loss. The resulting disruption at these junctions between brain cells impairs cellular communication. The loss of synapses has a strong correlation with cognitive decline in people with Alzheimer's disease.
Dr Ivan Koychev, Senior Clinical Researcher and co-author of the paper said: “This opens the door for effectively testing treatments in preclinical experiments through the tight link between the cell models and the patient population.”
Improving preclinical research to the point at which it is reproducible and translatable to clinical-trial success will be an extraordinary challenge. However, even if a few clinical successes find their way, then that will very well facilitate a discovery process that will lead to finding new therapeutic strategies for treating the disease.
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 includes DPAG, the Kavli Institute for Nanoscience Discovery, the Nuffield Department of Clinical Neurosciences, and the Department of Psychiatry.