Maybe Alzheimer's Isn't Inflammatory, So What Is To Blame?

We’re still very unclear about what causes Alzheimer’s disease. Because it affects the mind it’s a uniquely frightening prospect, and any news we can get on how it works or what we can do about it is a step in the right direction.

Trouble is, it looks like we might have gone a little in the wrong direction.

In Alzheimer’s, you find pieces of tissue in the brains of sufferers called amyloid plaques. These also show up in the brains of people with Parkinson’s and even the degenerative encephalopathic disease CJD. Are you thinking what I’m thinking?

You, and a lot of scientists. What if amyloid plaques are the causative agent? By somehow interfering with blood flow, or by some chemical effect, amyloid plaques could be the cause, or a crucial part of the mechanism of these diseases. Get rid of the plaques and you might be able to get rid of the symptoms.

Rather than amyloid plaques, the real cause of Alzheimer’s now appears to be something else altogether. Amyloid is a result, not a cause — it’s something else that happens to you when you have Alzheimer’s or other degenerative neurological diseases, but it’s not the main driving force.

Tau proteins are found all over the CNS but especially in the brain and they have a very specific job; they stabilize microtubules. As much as this sounds like something Doctor Who might struggle with during a particularly underfunded episode - pass me the sonic screwdriver, I have to stabilize this microtube! - it’s actually a desperately important function, because of the role that microtubules play in brain function.

Microtubules are a part of the structure of all your cells. They form the cell skeleton, or cytoskeleton. They’re hollow spirals made of protein copolymers and they do a range of jobs in addition to holding cells in shape, depending where you find them. Find them in the brain, and they’re holding the elongated, branched structures of neurons in their right shape and their right place.

When tau proteins stop supporting them properly, you’d expect them to start to collapse. The metabolic functions that depend on their ability to be stable and mobile would cease. And that is what happens. It happens in the cells with the most connections, which in humans is the neurons in the areas of the brain related to abstract thought, creativity, the creation of new ideas and the lawying down of new memories. Sounds right. And the effects are most devastating, most soon, in the neurons whose connections are still tentative where new memories are being laid down in long-term memory storage. That makes sense too, and it fits with what we know about the symptoms and progress of the disease.

But there's more to the damage Tau can do than which neurons are harmed first. The brain is divided into areas with specialist functions and it's this that has made the scientists behind the breakthough study, published in Brain in March of this year, recommend that research attention turn from amyloid to Tau. 

READ Misconception of Alzheimer's: Genetically Inherited or Not?

Abnormal Tau starts accumulating first in the hippocampus, the part of the brain that deals with memory, before moving to the cortex which deals with thought and ideas. Amyloid does the opposite. That's a strong argument that Tau is the real cause.

Where Next For Alzheimer's Treatment?

So if the Tau-ists are right, the door to an inflammatory-model treatment for Alzheimer's based on an anti-inflammatory diet and anti-inflammatory drugs aimed at reducing amyloid plaque as an inflammation by product slams shut. 

But do the Tau-ists open another door even as they close what once appeared to be a promising line of enquiry into Alzheimer's?

Maybe. There's a trial at Harvard under way right now that's screening patients for Tau as well as beta-amyloid, the specific amyloid responsible for plaques in the brain. And the transfer of attention from amyloid to Tau can't come quickly enough in the drugs industry. Pharmaceutical companies have developed drugs that target amyloid plaques and reduce the amount of beta-amyloid in the brain, but none of them has been able to show that it can affect the course of Alzheimer's. So shifting focus to Tau might mean we're at least working on the right problem.

And the work has already begun. As long ago as July of 2014, scientists at a conference in Copenhagen presented their plans for Tau-based therapies. Methods that are being explored include active vaccines, an antibody, an inhibitor that stops the enzyme that removes sugar molecules from Tau and an anti-aggregating compound. One therapy works by injecting antibodies that attack and clear Tau from the brain, while another the enzyme-based treatment is expected to be effective because Tau steadily sheds sugar as people age. Preventing Tau from shedding sugar is expected to restore Tau to the function it would have in a younger person and prevent the neuron damage that leads to Alzheimer's.

Some of these, including one of the vaccines, have already completed rounds of testing in mice and in almost every case human trials are under way. In some cases, these are working with groups of people who are suffering from diseases like progressive supranuclear palsy, which is a rare and fast-acting disease caused by Tau pathologies.

There's also hope that treatments that help Alzheimer's patients might be effective for a wide range of illnesses. If everything about the amyloid hypothesis is correct except whcih brain protein is to blame, then the raft of expectations that attached itself to amyloid therapies doesn't have to be abandoned. It can attach itse;f almost unchanged to Tau therapies. If Tau treatments work against Alzheimer's they might also be effective against Parkinson's or even CJD.

READ Is it Alzheimer or is it Low Blood Level of Vitamin B12?

If you like what you've read, or you think I've left out something crucial, get in touch in the comments section below.