#2170 - Max Lugavere

Max Lugavere (0:13)

I know.

Joe Rogan (0:14)

What's cracking?

Max Lugavere (0:16)

Oh, man, just first of all, honor to be here.

Joe Rogan (0:19)

Thank you.

Max Lugavere (0:19)

Love you and your work. And yeah, I mean, just national treasure.

Joe Rogan (0:25)

That's very nice of you.

Max Lugavere (0:26)

Go out on a limb and say it. But no, I'm super, super excited because I've been working on this documentary for the last 10 years of my life, and it's finally out today, which I'm super pumped for. It's called Little Empty Boxes. And we talked about it the last time I was here.

And it's a project that means the world to me. I think it's the most important thing I've ever done. And it's the first ever dementia prevention documentary about the science of dementia prevention. But it focuses. It's a very emotional and personal film for me because it follows my mom who for many years suffered from a rare form of dementia called Lewy body dementia, which is akin to having both Parkinson's disease and Alzheimer's disease at the same time.

Joe Rogan (1:07)

That's what Robin Williams had.

Max Lugavere (1:08)

That's what Robin Williams had, yeah. And it's a rare condition. It affects about one million people in the United States, but it's a dementia. And dementia is now a soaring public health problem.

And there's a lot of controversy within the field.

The last time I was here, we talked about fraud in the research space with regard to the prevailing hypothesis as to what causes Alzheimer's disease, which is the most common form of dementia. And actually finally, over the past month, that paper was finally retracted. It took two years.

Joe Rogan (1:45)

But... Could you explain to everybody what the fraud was?

Max Lugavere (1:49)

Yeah, so basically, among the dementias, Alzheimer's disease is the most common form of it, and that affects about six million people in the United States. And since it was first named in 1906 by physician Alois Alzheimer, the prevailing hypothesis as to what causes Alzheimer's disease, dubbed the amyloid hypothesis, has been that this plaque formed by a precursor protein called amyloid beta accumulates in the brain. And by finding a drug that can potentially remove, extract that those plaques from the brain, from the extracellular space around neurons, that we could essentially cure the disease, that the causal factor in the condition was ultimately this amyloid beta protein, which forms the plaque. And trial after trial had been a dismal failure, and it wasn't looking good until in 2006, a paper was published in Nature, which for any scientist publishing in Nature, it's like winning an Academy Award. And that paper, essentially, what that did was it allegedly identified this variant of amyloid beta that connected the plaque to the cognitive dysfunction. So the most important clinical feature of Alzheimer's disease, because for a long time, it was known that cognitively healthy people accumulate plaque in their brains. And that plaque doesn't seem to correlate with cognitive impairment or anything like that.

And so that was very deflating for researchers in the field until this 2006 paper came out. And what it did was it renewed faith in this hypothesis, which was always a hypothesis, and continued to send billions and billions of dollars worth of funding down this path. And what turned out to be the case just two years ago was that that paper was essentially fraudulent, and it represented about 16 years worth of wasted time, wasted money, which was hugely deflating for not just the research community, but also for any patient who's ever suffered from Alzheimer's disease.

And the way that the field is now slowly starting to turn, but this is a drum that I've been beating for the past 10 years, is that we really need to start talking about these conditions in terms of prevention. And that's what inspired me to set down this path of creating this documentary, Little Empty Boxes.

Joe Rogan (4:14)

What was the fraud? Like, how did they do it?

Max Lugavere (4:18)

So basically, in the paper, they identified these proteins that they isolated in rat models of the condition, mouse models of the condition, called A-beta-star-56.

Again, amyloid is there at the scene of the crime, so to speak. So when you have Alzheimer's disease, somebody who's died of Alzheimer's disease, what they find inevitably in the brains of cadavers who've died from Alzheimer's disease are two features. They see this aggregation of these plaques, amyloid beta plaques, and tangled proteins called tau. And so it was a very seductive narrative that this plaque causes the condition, right, for years. The problem is they've succeeded at reducing the plaque in the brains of people with Alzheimer's disease, but that hasn't led to any improvement in the clinically meaningful features of the disease that we aspire to improve for sufferers of Alzheimer's disease, right? The cognitive, the cognitive function.