Now Alzheimer's disease is an autoimmune disease? That's a switch!

In the few years that I've spent trying to understand Alzheimer's, one thing has impressed me above all else.  We just don't understand this disease.

Sure, we know that the Alzheimer's brain loses cells and atrophies.  Problems with tau protein cause the microtubules to collapse into tangles.  And we see amyloid plaques accumulate in ways that might impede memory and cognition.  Maybe they too can kill neurons.  Certainly what we notice most about the disease is what happens to people as the disease progresses--the deterioration of their memories, cognition, and even personhood.  That's what we notice, but are those effects central to the disease's dynamic?

We've written before about grave questions with our understanding about how these things happen.  There seem to be several genes involved in many (but not all) cases.  Do these genes cause the disease, or do they just create conditions in the brain that are fertile for the disease?  There is other evidence implicating a role in the disease for the herpes virus, and that seems to be an avenue to pursue.  But there is also evidence that a bacterium causing gum disease plays some kind of role.  Maybe the amyloid plaques are simply the body's defensive action to protect the brain from an invasion of bacteria?  There are many hypotheses.  Some fit together, while others suggest multiple, entirely different mechanisms of the disease.

So now there's another hypothesis.  Alzheimer's is actually an autoimmune disease, and we should be barking up that tree.  Where did that idea come from?

The idea comes from research published in Nature, one of the most prestigious scientific journals.  It was "Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy."  The research was conducted by a team led by Dr. David Holtzman of Washington University, St. Louis.

In Beating the Dementia Monster, we provided a rather simplistic explanation of the brain's immune system.  We said that the brain was isolated from the body's main immune system by the blood-brain barrier, and used its own immune cells, called microglia, to fight off any invading pathogens that succeed in crossing the blood-brain barrier.  It doesn't use T-cells or B-cells.

Or does it?  Dr. Holtzman's team found T-cells and evidence of T-cell activity in the brains of mice bred to imitate Alzheimer's disease.  They further found that they could halt brain atrophy by removing the T-cells.  The thought is that the T-cells are constantly being activated to respond to an antigen and are subsequently exhausted.  But there's a cycle in which the exhausted cells lay dormant for a while and are then reactivated.  But they're not that dormant, and the "dormant" cells can cause injury to surrounding cells.  

And why are they constantly being reactivated?  They weren't sure, but this seems to be where the autoimmune part comes in.

As we've said so many times before, mice are not people, and something we see in mice may not apply to people.  But in samples of brain tissue from people with different stages of Alzheimer's disease, the researchers found higher levels of T-cell presence in the more advanced stages.

So what does this all mean for Alzheimer's disease research?  As a minimum, it gives us a new avenue to pursue for understanding the disease.  But it also may be about to turn everything we think we know about the disease on its head.