Alzheimer’s and Pathogens: Changing how we understand the microbiome

Alzheimer's disease linked to pathogens

The following is a summary with excerpts from Aeon’s “A bug for Alzheimer’s?” which discusses how microbes may be implicated in a chronic brain disease. It may seem not so relevant to ME/CFS, but CII’s own Dr. Mady Hornig discusses the strategies and challenges associated with linking microbiome differences or infections (even infections outside the brain!) to complex brain disorders.

Alzheimer’s disease is poorly understood, but the current accepted theory is that it’s caused by the build-up of beta-amyloid plaques in the brain. To oversimplify, think of beta-amyloid as a gluey substance that kills off brain cells and eventually leads to the hallmark cognitive problems associated with Alzheimer’s. But, new research indicates that the currently-accepted theory of beta-amyloid plaques causing Alzheimer’s disease may not be correct.

Robert Moir, a neurologist at Massachusetts General Hospital in Boston, has a newly published theory that has the potential to reshape the way that we think about Alzheimer’s and dozens of other diseases. “The Pathogen Hypothesis” as they call it, suggests that “microbes play an important role in Alzheimer’s disease and that beta-amyloid plaques are actually soldiers in the body’s fight against them – a fight that eventually goes haywire, causing mass brain-cell death.” No longer a biological anomaly, the beta-amyloid plaques may be the result of the body fighting against pathogens.

This article (which is not meant to be an exhaustive scientific literature review) mentions pathogens potentially linked or related to Alzheimer’s including:

  • Lyme Disease
  • Chlamydia pneumoniae
  • HSV-1 (Herpes Simplex Virus 1)

Now, before anyone jumps to “now we just have to figure out which bacteria/virus causes Alzheimer’s, right?”, it doesn’t appear to be quite that simple. The research suggests less of a direct cause/effect relationship and more of a “triggering the start of a potential cascade” link between infections and Alzheimer’s.

“Most proponents of the pathogen hypothesis don’t suggest that infections work alone to cause Alzheimer’s disease, nor do they think that Alzheimer’s can be ‘caught’ like a cold. They instead argue that infections – perhaps a number of different types – can spark a cascade of events that, over time, can culminate in the disease. ‘These microbes might not serve as specific causes, per se, of the disease, but rather as contributors to a degenerative process,’ says Mady Hornig, director of translational research at Columbia University’s Center for Infection and Immunity.” – Melinda Wenner Moyer

Did you catch that? CII’s very own Dr. Mady Hornig was interviewed for this article! And, there are takeaways from this Alzheimer’s research that will likely resonate with the ME/CFS community.

Science means never having to say you’re sorry?

“Considering that the neurodegenerative process that leads to Alzheimer’s likely takes years, if not decades, and that it also involves other factors, it is not terribly surprising that the idea has been so difficult to accept. ‘We tend to gravitate toward parsimonious answers to complex questions in all walks of life, and our quest to solve the perplexing mysteries of neurodegenerative diseases is perhaps no different,’ Hornig explains. ‘Tracing the path from an infection to a disease as complex as Alzheimer’s requires substantial tolerance for caveats and an appreciation of how factors from the environment, including infections, might lead to different brain outcomes.’” – Melinda Wenner Moyer

The currently accepted model for Alzheimer’s disease may not be accurate. And, no one wants to face that. One of the biggest hurdles facing the pathogen hypothesis is that “conceding that the pathogen hypothesis has merit means admitting that the field has been wrong about Alzheimer’s for a very long time”.

Is anyone in the ME/CFS community nodding along in agreement yet?

Microglial activation

The mechanism behind Alzheimer’s is still not fully understood. But, if the latest research is on the right track, there is more to it than just the beta-amyloid plaques we talked about earlier.

“According to the amyloid cascade hypothesis, the brain’s accumulation of beta-amyloid plaques is the primary cause of sporadic Alzheimer’s disease. By this definition, then, brains overflowing with plaques should have Alzheimer’s. But often they don’t: postmortem studies show that one-quarter to one-third of non-Alzheimer’s-diseased elder brains are filled with amyloid plaques, too.

Interestingly, the behaviour of microglia, the brain’s resident immune cells, can in part distinguish these so-called ‘resilient’ brains from brains that have Alzheimer’s. In a 2013 study, researchers at Harvard University analysed 50 brains, some of which came from people who did not have Alzheimer’s yet had beta-amyloid plaques. They found that one key difference between the resilient brains and the diseased brains was that the former had much fewer activated microglia.” – Melinda Wenner Moyer

We recently reported on a Parkinson’s study that discussed this same concept of microglial activation. And yes, this idea of microglial inflammation has been suggested as linked to ME/CFS as well. More research is being done and even more is needed in these areas to better understand how microglial inflammation may or may not impact disease etiology and how we might be able to prevent or reverse it.

Ghost-virus hunting

As mentioned, researchers have found pathogenic links to Alzheimer’s in the past but are still sort of at the stage of chasing ghosts. And, if Alzheimer’s is actually just the end of the cascade caused by an infection, they may only be looking for the ghosts of an infection from years or decades past!

“‘Even a brain biopsy may fail to uncover an agent if it is present at very low levels – under the radar for detection, perhaps because samples are acquired in the wrong brain region or after the acute phase of the infection has resolved – or if it is a novel, unexpected agent,’ Hornig explains.” – Melinda Wenner Moyer

Yes, pathogen testing has been done in the brains of Alzheimer’s patients. As of right now, if a pathogen is responsible for Alzheimer’s disease we’re likely looking for it in the wrong place or at the wrong time. Even more confounding, if we don’t know what we’re looking for, as in the case of a previously-unknown pathogen, we might not be able to detect it even if it’s right in front of us the whole time!

Takeaways:

  • New research has linked microbes to Alzheimer’s disease
  • This doesn’t prove that an infection directly causes Alzheimer’s, research indicates a more complex path than that
  • Breaking through previously-accepted scientific theories and disease models is a battle
  • Pathogens are hard to find when we don’t already have a test for them, aren’t searching during the acute infection period, or aren’t looking in exactly the right place.

All quotes in this article are from Aeon’s “A bug for Alzheimer’s?” written by Melinda Wenner Moyer, 16 Jan. 2017.