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Do Bacteria Cause Alzheimer's?

Do Bacteria Cause Alzheimer's?

The Brain

More Information about Alzheimer's Disease http://www.alz.org/facts/
Additional Resource: “Are microbes stealing your mind?” By David Ewing Duncan, The Daily Beast

As cases of dementia rise with an aging population, a new company is exploring a controversial theory and novel solution

This article comes from an edited transcript of the Arc Fusion Talk delivered by Casey Lynch on April 21, 2015. Watch the video here.

The next hundred years of aging – what will it look like? My biggest fear is that our bodies are living longer and longer but our brains still have the same short half-life. This is the path we're on. You can see the rate of Alzheimer's going up and up as people are living longer. We may be able to avert that path. We may be able to treat brain disorders by refocusing what we're looking at and treat other disorders of aging by looking not just at human proteins but at the bacteria, the microbiome, living within us.

In 1982 the Australian physician and researcher Barry Marshall and his collaborator Robin Warren discovered that the bacteria H.pylori could be cultured from, and was a likely cause of, ulcers. This was met with extreme skepticism from the establishment because everybody knows that ulcers are caused by spicy food and stress. In 1984 he went so far as to drink a petri dish of the bacteria to prove his case. He got various GI symptoms and in 2005 the pair was awarded the Nobel prize for this discovery, and ulcers are now treated with antibiotics. This was a long path to prove his case.

Dr. Steven Domini is a UCSF psychiatrist with a specialization in HIV dementia. He knew pathogens can cause brain disorders. What other pathogens might be causing brain disorders? He called me in June 2013 and said “I think I've found a bacterial cause of Alzheimer's disease.” I'm an entrepreneur with a background in Alzheimer's research so I was intrigued.  Like many others I've been frustrated by the string of failures of Abeta [Amyloid beta] targeted therapy.

Abeta has been the focus of billions and billions of dollars and a huge amount of research. Ninety five percent of the money has gone into this target but most of the studies are failing, so I was excited about a novel approach. 

This is what Steve showed me. These are neurons and they've been stained for a toxic bacterial protein. This bacteria secretes enzymes which literally digest our cells for food. And this brown staining is showing that. These neurons are not very happy. They are falling apart. In a normal human we don't see this staining.

But we all know the difference between correlation and causation. Just because these bacterial protease are in human brains does not mean that they're causing Alzheimer's disease. So we set out to do a number of experiments to prove to ourselves and the rest of the community that this was indeed a credible theory and that we could develop treatments targeting it. The first thing we did was look at as many human brains as we could get our hands on. So far we've looked at 43 Alzheimer's patients and every single one of them has this bacterial protease in their brain. We've looked at 30 preclinical cases –  these are people with pathology but they're not diagnosed. – they also have it in their brain, every one of them.

In healthy people some people are clean but some people do have small levels of this bacteria and its proteases. We think those people are on a path either to Alzheimer's or maybe they just look like accelerated aging. We don't know yet. The other thing we did to prove causation is to infect mice. Bacteria gets into their brain, causes degeneration, causes cognitive dysfunction and triggers Abeta – this protein that everyone else has been obsessed with. 

We think natural aging creates these leakages in the blood brain barrier.  The bacterial load creates ligatures in the blood brain barrier. If you have any genetic risk, it can increase this leakiness, giving some people Alzheimer's disease. What about younger people? What if you had multiple concussions that increase the permeability of your blood brain barrier? You might get dementia in your 20s or 30s like some football players are ending up with.

We're working on a therapeutic. This particular bacteria is quite resistant to broad spectrum antibiotics.  The more we understand about the microbiome the more we know we don't want to wipe out all of these good bacteria. That just clears the way for the pathogens to take over. We're developing a very narrow spectrum antibiotic which also protects the site of toxicity of the bacteria.  This is a general approach. It's hard to discover these bacteria because they have imperfect penetrants. 

"So far we've looked at 43 Alzheimer's patients every single one of them has this bacterial protease in their brain."

Being infected in one area of your body might be fine, having a low level infection might be fine, but having a higher level in a different organ or in your brain clearly could cause more problems.  They have a very long lifecycle so these pathogens don't want to kill their host like Ebola for example. You don't get infected and then two weeks later you have symptoms and you die off. These pathogens are very tricky. They want their host to live a long time. They can hibernate. They can stay undercover for a long time. So the process of discovering them is going to be difficult but I'm really excited about the possibilities it presents. 

Casey Lynch is the CEO of Cortexyme and the Founder and Managing Director of NeuroInsights.