Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder,
responsible for nearly two-thirds of all dementia cases. In this review, we report the potential AD
treatment strategies focusing on natural polyphenol molecules (green chemistry) and more specifically
on the inhibition of polyphenol-induced amyloid aggregation/disaggregation pathways: in bulk and on
biosurfaces. We discuss how these pathways can potentially alter the structure at the early stages of AD,
hence delaying the aggregation of Aβ and tau. We also discuss multidisciplinary approaches, combining
experimental and modelling methods, that can better characterize the biochemical and biophysical
interactions between proteins and phenolic ligands. In addition to the surface-induced aggregation,
which can occur on surfaces where protein can interact with other proteins and polyphenols, we
suggest a new concept referred as “confinement stability”. Here. on the contrary, the adsorption
of Aβ and tau on biosurfaces other than Aβ- and tau-fibrils, e.g. red blood cells (RBCs), can lead
to confinement stability that minimizes the aggregation of Aβ and tau. Overall, these mechanisms
may participate directly or indirectly in mitigating neurodegenerative diseases, by preventing protein
self-association, slowing down the aggregation processes, and delaying the progression of AD