Tangled Path of Alzheimer’s-linked Brain Cells Mapped in Mice

Scientists at The Johns Hopkins University have succeeded in mapping cholinergic neurons, the first cells to degenerate in people with Alzheimer’s disease, in experiments on mice. Using genetic engineering methods, the research team programmed several cholinergic neurons per mouse to make a protein that could be seen with a colored chemical reaction. The team preserved the mouse brains and then thinly sliced them to produce serial images. The branching path of each neuron was then reconstructed from the serial images and analyzed. Although each cholinergic neuron, on average, contains approximately 1,000 branch points, they vary significantly in the extent of the territory that they cover. The researchers used the same techniques to study the cholinergic neurons of mice with a rodent form of Alzheimer’s disease and found that the branches were fragmented. They also found clumps of material that may have been debris from the disintegrating branches. Although the cholinergic neurons of human brains have not been individually traced, the team was able to calculate that the average cholinergic neuron in the human brain has a total branch length of approximately 100 meters. “That is a really long pipeline, especially if one considers that the pipes have diameters of only 30 thousandths of a millimeter, far narrower than a human hair,” says Jeremy Nathans, PhD. “Although our study only defined a few simple, physical properties of these neurons, such as size and shape, it has equipped us to form and test better hypotheses about what goes wrong with them during disease.” To learn more about the study, click here.