Researchers have developed a new method to gain insight into the development of Alzheimer's disease. The team of Professor Bart De Strooper (VIB–KU Leuven, Dementia Research Institute in the UK) transplanted human brain cells in mouse brains containing amyloid plaques, one of the hallmarks of Alzheimer's disease. They found that the transplanted human brain cells are much more susceptible to the disease than those of mice.

Studying the development of Alzheimer’s disease presents unique challenges, as brain cells behave differently in vivo and in vitro. Using mice as models presents useful insights but mouse models never fully develop the disease despite the fact that their brains and brain cells are quite similar to their human counterparts.

Researchers have now transplanted human brain cells into mouse brains that mimick some of the hallmarks of Alzheimer’s disease, including the presence of amyloid plaques. They found that, compared to mouse brain cells, human brain cells are much more sensitive to amyloid plaque pathology. This novel model allows for a better characterization of the disease processes that actually take place in the brain of human patients.

Much of the work was performed in close cooperation with Professor Pierre Vanderhaeghen (ULB–WELBIO, VIB–KU Leuven), whose lab previously pioneered the technology to differentiate human pluripotent stem cells into brain cells in vitro, and then transplant them in the mouse brain, generating a human/mouse chimera.

“We relied heavily on the insights and expertise of Pierre Vanderhaeghen and his lab to set up this new AD model," says Professor Bart De Strooper. "With this novel experimental technique, we can study how different cell types in the human brain respond to the Alzheimer's pathology and hopefully unravel the link between amyloid and tau protein pathology – which leads to neuron death and is the holy grail of current Alzheimer’s research.”

The study was published in the journal Neuron.