Hannah Fry: I lost my dad to Alzheimer’s. New research into its origins is amazing

I was sitting in a conference in August, drifting as I so often do between listening to what was on stage and pretending to be doing important work on my laptop (by which I mean sending memes on WhatsApp).

All of a sudden, from the stage, the renowned biologist Aviv Regev came out with a sentence that made every single person in the room sit up and pay attention: “Of course,” she said, “we now know that Alzheimer’s starts in the nose.”

I’m sorry, what? Starts in the nose? I didn’t know Alzheimer’s starts in the nose.

My own lovely dad died from Alzheimer’s last year, and ever since his diagnosis, I’ve done an incredible amount of digging into the disease, trying to understand what was happening to him. I was astonished I’d never come across this idea.

And perhaps you haven’t either. Which is why I want to share my astonishment at discovering that Aviv Regev was right – not only is Alzheimer’s closely associated with our sense of smell, but there is a growing body of research suggesting that our noses might have something to do with why the disease develops in the first place.

The first bit you might already know: people with Alzheimer’s tend to lose their sense of smell, sometimes years before any symptoms of memory loss start to show up. But it turns out that our ability to smell is a surprisingly good indicator of our overall health (looking at you, covid-19). One study from 2014 found that smell loss in older people was a better predictor of whether they would be dead within five years than a cancer diagnosis.

It’s not that losing your sense of smell itself will kill you. More that the olfactory nerves are deeply intertwined with some of the most important memory structures in the brain, so when they start to deteriorate, it can be an early warning that something much more serious is going on.

And this connection seems to work in both directions. One intriguing study (admittedly with quite a small sample size) put a diffuser with essential oils by older people’s beds, thus exposing them to all kinds of wonderful scents while they slept. After six months, the people who had the olfactory enrichment performed better on memory tests than those in a control group.

All very interesting. But not what Regev had been suggesting. Her words seemed to imply that noses are actually responsible for the trouble in the first place.

It turns out that the reason scientists are even entertaining this possibility is because of how fiercely our brains are protected from the outside world. Our skulls are like an actual fortress: even our blood isn’t allowed in without passing a particularly fussy bouncer called the blood-brain barrier.

One of the only real exceptions is a little bit of bone right at the top of your nose that is riddled with holes. It’s called the cribriform, and it’s where the olfactory fibres dangle down into your nose to give you your sense of smell – a bit like if you pushed some Play-Doh through a sieve.

And that means that, despite all the elaborate defences protecting your brain, there is a potential route in, sitting right in the middle of your face.

So, here’s the idea. Maybe the beta-amyloid plaques, the sticky little protein fragments that appear to play such a key role in the cascade of Alzheimer’s in the brain, are what’s left over after the brain has fought an infection. And maybe the nose is how the infection arrives.

To see if this held any water, in 2022, a group of scientists squirted some chlamydia up the noses of some mice.

(I should add, for the sake of the mice’s reputation, that it was actually Chlamydia pneumoniae, a cousin of the bacterium that causes the STI. But I hope you’ll forgive me the less scientifically accurate version. In a long career, you get very few chances to write sentences that good, and I wasn’t about to waste mine.)

The remarkable thing, though, was that within 72 hours, the bacteria had travelled up the nerves in the nasal cavity and got through to the brain. What’s more, the infection triggered the accumulation of beta-amyloid. Now that’s not definitive proof of how Alzheimer’s starts in humans. But there is some other, rather unsettling evidence that infections aren’t the only unwelcome visitors that manage to get in that way.

A group in Mexico studied stray dogs that spent their lives breathing in polluted air. Inside the dogs’ brains, they found microscopic particles of metals – that seem to have entered through the nose – wrapped in pockets of inflammation and that same beta-amyloid protein. You don’t see the same thing in dogs that lived in cleaner, more rural environments.

Now these studies have been extended to look at the brains of very small children and young adults who died from gun violence or car accidents – and they find something similar. Tiny, metal–rich particles, thought to originate from exhausts and brake dust, turned up in their brain tissue, alongside inflammation and accumulations of beta-amyloid. The very sorts of changes associated with Alzheimer’s, appearing in brains that were sometimes only a few years old. Put together, it implies that the disease might have an environmental cause, one that begins much much earlier than we thought.

So, where does Alzheimer’s start? The answer is no one nose (pun very much intended). There is still a great deal we don’t understand, but the implications from all this research are rather extraordinary. What if the beta-amyloid plaques we’ve spent so long trying to get rid of are, at least sometimes, the aftermath of the brain trying to protect itself? And what if, rather than focusing entirely on clearing up the damage, we could work out what set it off in the first place?

But more than anything, I can’t help but laugh as I think about all this in the context of my dad, who had many wonderful qualities, but a discreet nose wasn’t one of them. We used to say that his nose would enter a room 15 minutes before he did. He would have found it very funny indeed if it turned out to have been the cause of his downfall.