In a feat that could help unlock greater understanding of Alzheimer's disease, Johns Hopkins scientists have traced the pathway of nerve cells linked to the debilitating condition.
The findings reveal the pathways of some of the largest nerve cells in the mammalian brain nerve, called cholinergic neurons, which are the first to degenerate in the brains of people with Alzheimer's disease.
"Each of these cells is like a city connected to its suburbs by a single, one-lane road, with all of the emergency services located only in the city," said Jeremy Nathans, a professor of molecular biology and genetics, neuroscience and ophthalmology at Johns Hopkins University School of Medicine. "You can imagine how hard it would be in a crisis if all of the emergency vehicles had to get to the suburbs along that one road. We think something like this might be happening when cholinergic neurons are trying to repair the damage done by Alzheimer's disease."
In mice, Nathans and his team plotted these complex paths by genetically engineering several cholinergic neurons per mouse to make a protein that could be seen with a colored chemical reaction.
The size and shape of the complex paths of these neurons, which have approximately 1,000 branch points, previously had been unknown to scientists. In normal mice--those that did not have Alzheimer's--the investigators found that the average length of the branches of a single cholinergic neuron, lined up end to end, is 12 in, varying from 4 in to 19 in. The average length of a mouse brain is just shy of 1 in.
In mice with a rodent form of Alzheimer's disease, cholinergic neurons in the brain looked much different. The researchers found that the branches were fragmented, possibly causing clumps of debris also found in the mice's brains.
The cholinergic neurons of human brains have not been individually traced, but Nathans estimates that the average cholinergic neuron in the human brain has a total branch length of approximately 100 meters, a bit longer than a football field.
The research, which may help scientists develop treatments for Alzheimer's disease, was published online in the journal eLife.
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- see the study abstract