The brains of patients with Alzheimer’s disease accumulate both amyloid plaques and tangles of a virus-like protein called tau. Recent experiments have revealed that tau, and not amyloid, is responsible for causing the symptoms that characterize the affliction. And a new drug currently in development may be able to stop tau in its tracks, which would mean significant progress in the fight against Alzheimer’s disease.
Narrator : Alzheimer’s has been a puzzle for a long time. You see, inside the brains of patients with the disease are two types of abnormally folded proteins—but no one knows which one’s responsible for the devastating symptoms.
Reisa Sperling : One is the build-up of amyloid into plaques. And the other is what we call tangles that accumulate inside the nerve cells.
Narrator : Tangles are composed of a protein called tau . Think of tau as part of the cell’s architecture, which helps stabilize neurons and allows them to communicate. Yet, in Alzheimer’s disease, tau clumps into toxic tangles, and neurons die.
Ken Kosik : For a long time, it wasn’t clear if the amyloid or tau were responsible for Alzheimer’s disease. Because both of them are hallmarks for the disease, so which is cause and which is effect? And for a long, long time, amyloid looked like the culprit.
Narrator : Other types of dementia—like a disease called PSP—started providing clues about Alzheimer’s, by turning the focus on tau .
Bruce Miller : PSP is caused by tau . Every symptom that a patient gets with PSP is driven by where tau deposits in the brain. So suddenly we could give meaning to the tau protein. We learned that if you have abnormal tau , you will get sick. You will get sick with 100% certainty.
Narrator : The implications were huge. Tangles—not plaques—may be what’s responsible for ravaging the brains of patients with Alzheimer’s. Abnormal tau , even without amyloid, could be deadly.
But how does it wreak its havoc? In a stunning experiment, Marc Diamond exposed healthy cells to corrupted tau , and then used an electron microscope to see what happened.
Diamond : So here’s a picture of these large accumulations of tau , sort of attacking the cell surface. And the cell has actually started to rearrange itself to capture them.
And what we saw was remarkable. The normal form of the tau within a day or so converted to the abnormal form inside the cell.
Narrator : The bad tau then escaped and invaded a neighboring cell, just like a pathogen. Its spread from neuron to neuron finally explained tau diseases, including Alzheimer’s.
Miller : All of a sudden, we have a totally new way of thinking about how to treat Alzheimer’s disease. Abnormal tau is the target. We’ve gotta get rid of the tau .
Narrator : And by comparing amyloid and tau scans in the same person, one thing is quite clear.
Sperling : In Alzheimer’s disease, people don’t get tangles spreading throughout their brain unless they have amyloid. So currently we think that amyloid pulls the trigger and tau is the bullet that unfortunately kills the nerve cells.
Rudy Tanzi : If you want to treat a patient who has Alzheimer’s disease right now, you have to treat the tangles. You had to treat the amyloid ten years before. If you’re suffering from this disease right now, you have to hit the tangles. The tangles are killing the nerve cells.
Narrator : To stop the spread of tangles, David Holtzman has developed a drug, or antibody, to target tau as it moves between neurons. And he’s tested it in mice.
David Holtzman : These mice develop tau pathology starting at, let’s say, about five months of age. So we gave the antibody from six months of age, all the way to nine months of age, a point at which we knew all the animals would have a lot of tau pathology in their brain.
Diamond : The initial results were unbelievable. It was obvious to anyone looking at the mouse’s brains that in one group the pathology was much less than in the other.
Narrator : Look at the treated mouse on the left, compared to the untreated mouse, which has a hard time moving as the tangles attack its brain.
If Holtzman’s drug can stop the spread of tau , it might just help in the development of a therapy for Alzheimer’s disease as well.
One step at a time, though. First, the drug has to be tested in human patients.
- Production & Editing
- Seeta Joseph & Ari Daniel
- Ari Daniel
- Sequence Producer & Director
- Sarah Holt
- Director of Photography
- Stephen McCarthy
- Adriano Bravo & David Kerins
- Jellyfish Pictures
- Original Footage
- © WGBH Educational Foundation 2016
- Additional Visuals
Daniel Margulies, Max Planck Institute for Human Cognitive and Brain Sciences
Tamily Weissman/Livet et al, Nature 2007
- Special Thanks
- Tangled Bank Studios
- (main image: Shutterstock/SpeedKingz)
- © WGBH Educational Foundation 2016