Cocoa Extracts Reduce Oligomerization of Amyloid-β: Implications for Cognitive Improvement in Alzheimer's Disease

Background: Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder, characterized by pathological aggregates of amyloid peptide-beta (A beta) and tau protein. Currently available therapies mediate AD symptoms without modifying disease progression. Polyphenol-rich diets are reported to reduce the risk for AD. Objective: In the present study, we investigated the AD disease-modifying effects of cocoa, a rich source of flavanols, which are a class of polyphenols. We hypothesized that cocoa extracts interfere with amyloid-beta oligomerization to prevent synaptic deficits. Methods: We tested the effects of three different cocoa extracts, viz. Natural, Dutched, and Lavado extracts, on A beta(42) and A beta(40) oligomerization, using photo-induced cross-linking of unmodified proteins technique. To assess the effects of cocoa extracts on synaptic function, we measured long term potentiation in mouse brain hippocampal slices exposed to oligomeric A beta. Results: Our results indicate that cocoa extracts are effective in preventing the oligomerization of A beta, with Lavado extract being most effective. Lavado extract, but not Dutched extract, was effective in restoring the long term potentiation response reduced by oligomeric A beta. Conclusion: Our findings indicate that cocoa extracts have multiple disease-modifying properties in AD and present a promising route of therapeutic and/or preventative initiatives.