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Alzheimer's, Parkinson's,
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and dementia are some of
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the most tragic consequences of aging.
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And we’ve had to accept them as inevitable,
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because we’ve had no other choice.
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But that might be changing,
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because these conditions
could have a surprising cause:
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common infections like the flu.
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In other words,
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these diseases may not be
something we have to accept
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as part of getting older --
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we might be able to prevent them.
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Now, to be clear, the flu virus does not
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suddenly give people Alzheimer’s.
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It gives people the flu.
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And Alzheimer’s is not infectious.
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You can’t catch Alzheimer’s
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the way you can catch the flu or mono.
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That’s because Alzheimer’s,
Parkinson’s, and dementia
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all belong to a family of chronic diseases
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that are caused by a build-up of protein gunk
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in our brain and nervous system.
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They’re called neurodegenerative diseases,
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or NDDs.
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But when researchers look back into history,
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they start to see some odd trends.
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A few years after big virus outbreaks
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like the 1918 flu pandemic,
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they would keep seeing surges
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in “Parkinsonism,”
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or symptoms like Parkinson’s.
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Since then, a constellation of links
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between infections and NDDs has been growing –
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it seems like when a severe infection happens,
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an NDD becomes more likely to follow.
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But those links are both really
hard to pin down and hotly debated.
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Here's how we're connecting the dots and maybe,
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just maybe,
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kicking some of our most devastating diseases to
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the curb.
[INTRO]
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Establishing for sure that the flu or mono
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causes Alzheimer's is super
ridiculously difficult.
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Like I said, the flu virus causes the flu,
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the mono virus causes mono,
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and the shingles virus causes shingles.
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Well, and chickenpox.
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So saying they also cause Alzheimer’s
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might seem like a totally wild take.
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We’ll get to how it might happen in a little bit,
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but the main thing epidemiologists want to see is:
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Does X cause Y?
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They can worry about the
how once they know the what.
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And, yes, viral infections might cause NDDs.
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At least, an association between the two
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is starting to show up everywhere you look.
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So far, the links are still fuzzy.
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But there are very specific elements researchers
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know to look for in order to prove
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that a specific factor causes a specific disease.
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The first thing you have to
do is nail down the timeline.
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It seems obvious,
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but historically,
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one of the most important and challenging parts
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of figuring out whether infections cause NDDs
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has been establishing that people
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had the viruses first.
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Because we can’t say viruses
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are causing NDDs if the patients
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already had Alzheimer’s
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before they got infected.
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That isn’t how time works.
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Luckily, figuring this out got a whole lot easier
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with the rise of electronic health records.
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In 2023, a study published in the journal Cell
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analyzed health records
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from over three hundred thousand people
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thanks to a massive database in Finland.
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That’s a lot of people.
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They identified patients with
a bunch of different NDDs —
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Alzheimer’s, dementia,
Parkinson’s, ALS, and so on.
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Then, the researchers looked up to 15 years back
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in their record for any severe viral infections.
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We’re talking flu, mono, pneumonia, herpes,
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stomach viruses, shingles, and more.
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Then they compared that group
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to people who also had an infection
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but were never diagnosed with an NDD.
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The results were striking.
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They found 45 viral exposures
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which significantly increased risk
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for developing an NDD in the future.
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And that’s interesting.
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But if the research team stopped there,
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their results probably
wouldn’t be super trustworthy.
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See, both these infections, like flu,
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and many NDDs, like Alzheimer’s,
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are all really common.
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And when you take a bunch of really common things
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and do some statistics at them,
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the math is sometimes going to come up as a match
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by pure, random chance.
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A tiny bit like those infinite monkeys
coming up with the text of Hamlet.
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It’ll happen eventually.
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In statistics, this practice is called “fishing”
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because you’re casting a really wide
net to “fish” for significant results.
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That means some of those 45 associations
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were probably not actually real.
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So, the team turned to a different
huge database of health records,
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this one from the UK.
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They successfully reproduced
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22 of the original 45 associations
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from that dataset,
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suggesting there might well be something to them.
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The strongest association was
between viral encephalitis,
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a virus causing inflammation
in the brain, and Alzheimer’s.
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It showed that being hospitalized
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with encephalitis increased someone’s risk
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for developing Alzheimer’s by 22 to 30 times.
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Reproducing their findings with data
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from a different country is a great start,
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but what is maybe even more persuasive
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is the number of other researchers
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that have independently
come to the same conclusion
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about viruses and NDDs.
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Researchers have found similar links
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between mono and multiple sclerosis,
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mono and Alzheimer’s, and flu and Parkinson’s.
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So, the evidence is building for links
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between viruses and neurodegeneration,
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but that’s still not rock solid proof
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that viruses are causing neurodegeneration.
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It’s just that this connection
is really hard to study.
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These NDDs seem to pop up
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between 1 and 15 years
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after the infection.
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That’s a long time to keep track
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of hundreds of thousands of people.
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The gold standard of proof
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would be some kind of clinical
trial where we’d find people,
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infect them with a virus,
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and then watch them in a controlled environment
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to see if they develop Parkinson’s or something.
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And while a study like that has actually
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been done successfully in rats,
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you cannot do that in people and should not try.
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So public health researchers
instead use real world data
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to make observations.
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For instance, several studies have shown
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that getting vaccinated for the
flu, shingles, and pneumonia
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can reduce the risk of developing
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Alzheimer’s and Parkinson’s.
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That tells us a few important things.
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First, while vaccines don’t
prevent all cases of infection,
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they can dramatically reduce the
severity of those infections.
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And that’s important, because that big study
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we were talking about earlier with
hundreds of thousands of people —
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that was looking at hospital data.
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And since you usually don’t
check into the hospital
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when you have the flu,
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that means we’re talking about severe infections.
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Vaccines are available for several of the viruses
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they looked at including
flu, shingles, and pneumonia.
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And they’ve all been shown
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to reduce infection severity
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or rates of hospitalization.
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So it could be getting severe infections
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leads to higher odds of
developing an NDD later in life.
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It also means we may be able to
prevent people from developing NDDs
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with a few safe, routine shots.
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So the question remains,
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if viruses cause NDDs,
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why and how do they do that?
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Why would a stomach virus so nasty
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you end up in the hospital cause problems
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for your brain?
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And not right away,
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but 15 years later?
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Having a plausible explanation
is not strictly necessary
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for establishing that viruses cause NDDs,
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but it does make researchers’ job easier
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when you get to the prevention part.
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So, to start off,
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it’s not unheard of for viruses
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to cause a chronic, non-infectious disease.
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Human papillomavirus is well known to
cause cervical cancer, for example.
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But we’re looking at a
bunch of different viruses –
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flu, shingles, mono, herpes —
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leading to a bunch of similar NDDs.
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It’s weird that they seem
to end up in the same place.
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It could happen a bunch of ways and
might be different for each virus,
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but here are two of the explanations
researchers have put forward.
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First, remember that all NDDs are caused
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by a build-up of protein
gunk in our nervous system.
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And second, all of these
viruses can be neurotropic,
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meaning they can enter and infect cells
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in our brain and nervous system.
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Of particular note is herpes, or HSV-1.
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Over 60% of the adult population in the US
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is estimated to have herpes.
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Most of the time you hear about herpes
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it’s because of the painful
sores it can periodically cause
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on people’s lips and eyes.
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In between flare-ups,
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the herpes virus lays dormant
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in our peripheral nervous system.
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Tons of things, from stress to sunlight —
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and even other infections —
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can reactivate the virus,
producing more baby viruses
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that travel down to the
skin and cause sores again.
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But those new viruses can also
migrate the other direction
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from the nerves in our skin up to the brain.
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HSV-1 infections in the brain are
usually completely asymptomatic,
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but even mild brain infections
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can be harmful and HSV-1 seems to linger …
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forever.
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And in mice, anytime those
dormant viruses re-activate,
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they for some reason ramp up
production of the same toxic proteins
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that make up the plaques in Alzheimer’s patients,
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essentially accelerating neurodegeneration.
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Since both herpes and all
those other viruses are common,
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severe bouts with the flu or shingles
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may be repeatedly triggering
mild herpes infections
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in the brain,
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which could help explain why NDDs
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are correlated with so many different viruses.
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So… it’s all herpes’ fault.
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Maybe.
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The other proposed mechanism
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has to do with the molecular cause of NDDs.
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One thing viruses and NDDs have in common
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is that they both make big
protein complexes in our cells.
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For viruses, those complexes are new baby viruses,
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but in NDDs they’re globs of smaller proteins
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all stuck together in our nervous system.
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For viruses to replicate,
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they need to hijack our cellular machinery
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to assemble new viruses.
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But it’s possible the changes they make
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to our cellular machinery
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could linger even
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after the viruses stop replicating.
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The faulty cellular machinery could,
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you might say, get confused.
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It’s now programmed to assemble proteins
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into new viruses,
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but it’s all out of virus.
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Instead, they might accidentally start
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globbing human proteins together…
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improperly creating those
harmful plaques that cause NDDs.
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One study,
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which hasn’t been through
the peer review process yet
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as we’re writing this,
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does present some early
evidence supporting this idea.
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The study shows that a drug
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that was originally designed to
interrupt the assembly of HIV viruses
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can also slow the assembly of
plaques in patients with ALS.
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So, maybe those plaques
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are being put together in a similar way,
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and the drug is resetting the faulty machinery.
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These ideas require further study,
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but they lend some weight to the notion
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that viruses are causing NDDs.
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All in all, while it’s still up in the air,
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the growing body of research
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certainly checks a lot of the
boxes epidemiologists look for
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when declaring a “causative relationship.”
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And we might get clarity on this
relationship in the coming years.
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The world is reeling from the COVID-19 pandemic
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caused by SARS-CoV-2,
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a virus that can infect the brain.
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And if severe viral infections
really do cause NDDs,
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then we would expect
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to see an uptick in Alzheimer’s and Parkinson’s
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over the next 10 to 15 years.
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Some papers suggest it’s already happening,
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but like all science,
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we need to wait for many researchers
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to come to that same conclusion
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before we make that call.
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Time will tell.
Now maybe this seems like terrible news.
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We all get the flu! We all get mono,
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and we all get herpes!
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So how does knowing they might be causing NDDs
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make any difference?
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Because knowing that viruses
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may be partially causing some of the most
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devastating diseases humans
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experience empowers us to find solutions.
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We’ve learned that vaccines for common viruses
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seem to protect us from NDDs.
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Those vaccines prevent severe infections,
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and severity appears to be a factor.
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There are also other ways
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to reduce the severity of some infections –
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like Tamiflu for flu, or Paxlovid for COVID-19.
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And while not all of these viruses have
vaccines yet, they’re working on it.
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For all of history, Alzheimer’s, Parkinson’s,
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and dementia have felt like
almost unavoidable problems
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we have to accept as we age.
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What if that’s not the case?
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What if these heartbreaking diseases
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have such easy-to-tackle causes
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that we could be on the
verge of getting rid of them…
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at least some of them?
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It’s not going to happen
next year, or in five years,
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but if these associations with
infections turn out to be real,
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we suddenly have a massive toolkit
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for dealing with neurodegenerative diseases.
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Vaccines and treatments
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that we already know are safe and effective.
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C’mon, science. Give us this one.
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[ OUTRO ]
