The Effects of Resveratrol, Caffeine, β‐Carotene, and Epigallocatechin Gallate (EGCG) on Amyloid‐β25--35 Aggregation in Synthetic Brain Membranes

SCOPE: Alzheimer's disease is a neurodegenerative condition marked by the formation and aggregation of amyloid-β (Aβ) peptides. There exists, to this day, no cure or effective prevention for the disease; however, there is evidence that a healthy diet and certain food products can slow down first occurrence and progression. To investigate if food ingredients can interact with peptide aggregates, synthetic membranes that contained aggregates consisting of cross-β sheets of the membrane active fragment A ${\beta }_{25\text{--}35}$ are prepared. METHODS AND RESULTS: The impact of resveratrol, found in grapes, caffeine, the main active ingredient in coffee, β-carotene, found in orange fruits and vegetables, and epigallocatechin gallate (EGCG), a component of green tea, on the size and volume fraction of Aβ aggregates is studied using optical and fluorescence microscopy, X-ray diffraction, UV-vis spectroscopy, and molecular dynamics simulations. All compounds are membrane active and spontaneously partitioned in the synthetic brain membranes. While resveratrol and caffeine lead to membrane thickening and reduced membrane fluidity, β-carotene and EGCG preserve or increase fluidity. CONCLUSION: Resveratrol and caffeine do not reduce the volume fraction of peptide aggregates while β-carotene significantly reduces plaque size. Interestingly, EGCG dissolves peptide aggregates and significantly decreases the corresponding cross-β and β-sheet signals.