Espresso Coffee Mitigates Aggregation and Condensation of Alzheimer’s Protein in Lab Experiments

Espresso coffee is among the most consumed beverages in the world. Recent studies report a protective activity of the coffee beverage against neurodegenerative disorders such as Alzheimer’s disease. Alzheimer’s disease belongs to a group of disorders, called tauopathies, which are characterized by the accumulation of the tau protein in fibrillar aggregates. In new research, scientists at the University of Verona characterized the molecular composition of the espresso coffee extract and identified its main components. With in vitro and in cell experiments, they demonstrated that the whole coffee extract, caffeine, and genistein have biological properties in preventing aggregation, condensation, and seeding activity of the repeat region of tau. They also identified a set of coffee compounds capable of binding to preformed tau fibrils.

Using NMR-based analysis, Tira et al. were able to identify the most abundant constituents of espresso coffee. Image credit: Sci.News.

Using NMR-based analysis, Tira et al. were able to identify the most abundant constituents of espresso coffee. Image credit: Sci.News.

Espresso coffee is among the best known beverages worldwide, and drinking espresso has become a habit in many countries due to its pleasant taste.

For many years, coffee consumption was associated with health risks. However, recent studies showed that when consumed in moderation, this soft drink could have beneficial effects on human health thanks to its biological properties.

The analysis and review of observational studies present in the literature suggest that consuming coffee could be advantageous against a number of chronic diseases, including some cancers, metabolic diseases, and neurological disorders such as Parkinson’s disease, Alzheimer’s disease, and depression.

In particular, numerous studies report that moderate and, sometimes, even high coffee consumption exerts a neuroprotective action against two of the most common neurodegenerative diseases, i.e., Parkinson’s and Alzheimer’s.

Many coffee compounds display beneficial properties in alleviating disease symptoms, for instance by reducing cognitive and memory impairment, as antioxidants, or by preventing amyloid formation and neurotoxicity.

The coffee beverage consists of more than a thousand compounds; the beverage as a whole and its components show a bioactive role, and therefore, coffee is considered a potential functional food.

University of Verona researcher Mariapina D’Onofrio and colleagues wanted to see if compounds in espresso could prevent tau aggregation in vitro.

They pulled espresso shots from store-bought beans, then characterized their chemical makeup using nuclear magnetic resonance spectroscopy.

They chose caffeine and trigonelline, both alkaloids, the flavonoid genistein and theobromine, a compound also found in chocolate, to focus on in further experiments.

These molecules, along with the complete espresso extract, were incubated alongside a shortened form of the tau protein for up to 40 hours.

As the concentration of espresso extract, caffeine or genistein increased, fibrils were shorter and didn’t form larger sheets, with the complete extract showing the most dramatic results.

Shortened fibrils were found to be non-toxic to cells, and they did not act as ‘seeds’ for further aggregation.

In other experiments, the researchers observed that caffeine and the espresso extract could both bind pre-formed tau fibrils.

Although much more research is needed, the preliminary findings could pave the way toward finding or designing other bioactive compounds against neurodegenerative diseases, including Alzheimer’s.

“We show that aggregation of the tau protein is modulated by espresso coffee extract and some of its components, at both concentrations used in the experiments (i.e., 50 and 400 μg/mL),” the authors said.

“Intraneuronal tau concentration has been estimated to be about 2 μM, 25 times less than what we have used in our experiments.”

“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.”

“In conclusion, we have presented a large body of evidence that espresso coffee, a widely consumed beverage, is a source of natural compounds showing beneficial properties in ameliorating tau-related pathologies.”

“Our findings could pave the way for further investigation into the design of bioactive compounds in the prevention and treatment of tauopathies.”

The findings were published online July 19, 2023 in the Journal of Agricultural and Food Chemistry.

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Roberto Tira et al. Espresso Coffee Mitigates the Aggregation and Condensation of Alzheimer’s Associated Tau Protein. J. Agric. Food Chem, published online July 19, 2023; doi: 10.1021/acs.jafc.3c01072

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