Espresso delivers smackdown to Alzheimer's proteins in lab tests
A nice strong cup of espresso is great for clearing the cobwebs out of the brain first thing in the morning. It might also be good for clearing Alzheimer's-causing protein tangles away too if lab tests hold up in further research.
When it comes to unraveling the mechanisms by which Alzheimer's disease operates, researchers have homed in on two problematic proteins: tau and beta-amyloid. These compounds, when they malfunction, are responsible for causing plaques and tangles in the brain that impair its function and lead to the cognitive decline associated with Alzheimer's.
In trying to combat the disease, we've seen a lot of research go into keeping tau and beta-amyloid from building up in the brain, with mixed success. After a failed test of a drug in 2022 that was meant to improve Alzheimer's symptoms by reducing amyloid in the brain for example, a more recent Phase 3 clinical trial on a different drug has shown promise.
In terms of better understanding tau's role in the disease, researchers have known that the substance, which normally helps nutrient-delivering microtubules to keep their shape, can sometimes get folded into shapes that cause it to clump and form tangles.
Building on previous research, in 2021, researchers from China and Australia figured out that tau tangles act like seeds that can spread to other neurons by commandeering a cell component known as the lysosome to break through the walls of the cell membranes in which they are encapsulated in structures known as exosomes.
“In people with Alzheimer’s disease, it seems the … exosomes trigger a reaction which punches holes in the wall of their own cell membrane and allows the toxic seeds to escape,” said Jürgen Götz, lead author of that study. “These leaks create a damaging seeding process that causes tau tangles and ultimately lead to memory loss and other impairments.”
Despite findings that have linked our gut bacteria to tau buildup and tests that have been able to identify tau through blood tests and spinal fluid analysis, a definitive way to eliminate the tangles associated with Alzheimer's disease has remained elusive.
Make mine a double
Now researchers at the University of Verona in Italy may have uncovered a way forward on this front – and it might be as simple as a shot of espresso.
In a study conducted by the Italian team, both a complete espresso extract as well as various compounds isolated from the drink including caffeine, trigonelline, genistein, and theobromine were tested to see how they interact with tau protein tangles known as fibrils. It was found that caffeine and genistein, an antioxidant known as a flavonoid, prevented tau protein clumps known as fibrils from forming long strands. This, in turn, prevented them from weaving themselves into the larger sheets that disrupt brain function. It also rendered the fibrils non-toxic and took away their ability to act as seeds and spread to other cells.
Caffeine was further shown to bind to existing fibrils which, the researchers say, could open the door to further investigation of using the compound either as a therapeutic or a potential test for the presence of tau.
While caffeine and genistein had the ability to keep the fibrils short, the full espresso extract had the biggest impact on tau. Because many of the compounds in coffee can cross the blood-brain barrier, the researchers believe that simply drinking espresso might convey some of the same benefits seen in the study.
"Based on the bioavailability of coffee components in the brain, and on the results of our study, we expect that moderate coffee consumption may provide a sufficient amount of bioactive molecules to act separately or synergistically as modulators of tau protein aggregation and toxicity," write the researchers. Of course, further research will be needed to see if the tests, which were conducted both on the isolated compounds and on live cells in lab dishes, will carry over to studies in animals and humans.
The study has been published in the Journal of Agricultural and Food Chemistry.