Amyloid plaques and tau tangles from an Alzheimer's brain
There’s been a lot of excitement over a paper that suggests a surprising way Alzheimer’s may progress in the brain. Based on work on a unique mouse model, researchers suggest that at least one of the abnormalities that drives the disease may spread from nerve cell to nerve cell like a virus.
That’s a stunning proposal, since there are only rare examples that proteins in the brain can “spread” in this way, aside from actual infectious agents like viruses or bacteria.
So it’s worth taking a closer look at exactly what the researchers mean by “spread.” For most of us, the concept conjures up something that is physically transmitted or passed on from one thing — in this case a cell — to another. Indeed, in their paper, published in PLoS One, the scientists describe a novel mouse strain that was genetically engineered to carry the human version of the gene for tau, which is one of two major proteins that builds up in the brains of Alzheimer’s patients. Not only did the mice express tau in the same regions of the brain as humans do, but, the scientists say, they saw tau appear in cells that weren’t engineered to contain the gene. Plus, these cells were connected to the cells that were.
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Their conclusion? That tau was somehow being transmitted from one cell to the other, propagating the destruction of neural networks as it went along. Aberrant versions of tau are the first signs that the physical architecture of neural networks is starting to degrade, eventually causing them to splinter into strands of dying nerve fibers that become entangled like disordered loops of wire. By looking at the presence of tau in the mice at different times, the researchers suggest that tau abnormalities spread like a contagion from cell to cell, thus causing the global breakdown of neural communication that eventually leads to cognitive losses.
But how sure can they be that tau is moving from cell to cell? Couldn’t the appearance of tau in different parts of the brain also be the result of some global deficit behind Alzheimer’s that causes the breakdown of the nerve networks? “It’s an interesting observation,” says Dr. Bill Thies, chief medical and scientific officer at the Alzheimer’s Association, “but it doesn’t really tell us whether there is any kind of movement of tau from one cell to another. It may simply be explained by the fact that one cell dying causes enough perturbation in the neighborhood that the next cell becomes disordered as well.”
Karen Duff, a professor at the Taub Institute for Alzheimer’s Disease Research at Columbia University and lead author of the paper, acknowledges that environment could be playing a role in where tau appears in the brains of the mice. But she says the animals were bred to express human tau in only one part of the brain, and that human tau’s appearance in other parts of the brain therefore strongly suggest the protein jumped, or transferred somehow from cell to cell. Supporting her case, she says, is precedent from Parkinson’s models showing that a protein critical to that neurodegenerative disease, synuclein, also moves from cell to cell. “We designed experiments to tell if the cell is upregulating its own production of tau, as a result of being in the same environment of the cells making human tau,” she says. “And we came to the conclusion that the tau was spreading. We suspect that the original cell dies, and the tau is picked up by neighboring cells.”
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But what Duff and her team believe is happening is novel on several levels. First, they propose that the tau is being passed from cell to cell, and with, destruction of the nerve’s architecture. Second, they propose that once inside a cell, the abnormal tau is somehow usurping the normal tau and turning it rogue, thus perpetuating the disease process in a technique called templating. The abnormal tau then serves as a seed, spreading to connected cells.
If that’s true, then the most breathless result from this work would be a drug that could stop the tau contagion, much like an antibiotic or antiviral are designed to thwart bacteria and viruses from their infectious mission. If tau’s diseased form can jump from cell to cell, then blocking that infectious leaping could put a halt to the slow cognitive decline that robs Alzheimer’s patients of their minds, personality and lives.
But all of this is still theory. Duff says she has not yet studied whether the mice with human tau show cognitive impairment. And these mice also exhibit only one part of Alzheimer’s pathology — the tau tangles — so their brains don’t have the build up of amyloid plaques, which researchers believe is the initial trigger necessary for the disease, meaning it’s possible the tau may be acting in a way it doesn’t normally in the presence of amyloid. In addition, the scientists have yet to look at whether levels of tau normally made by the mice are affected by the presence of human tau, and whether the human tau was indeed templating and changing the mouse tau. “We need a lot more studies to look into that,” says Duff. But that’s how science progresses. “Like most basic science, the paper answers one question but leaves you with two to three new ones,” says Thies. “We should never forget that a mouse is not a person.”
Alice Park is a writer at TIME. Find her on Twitter at @aliceparkny . You can also continue the discussion on TIME’s Facebook page and on Twitter at @TIME.