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

Article type: Research Article

Authors: Wang, Jun^{a; c; 1} | Varghese, Merina^{a; 1} | Ono, Kenjiro^d | Yamada, Masahito^d | Levine, Samara^a | Tzavaras, Nikos^b | Gong, Bing^a | Hurst, William J.^e | Blitzer, Robert D.^b | Pasinetti, Giulio Maria^{a; c; *}

Affiliations: [a] Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA | [b] Department of Pharmacology and System Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA | [c] Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA | [d] Department of Neurology and Neurobiology and Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan | [e] The Hershey Center of Health and Nutrition, The Hershey Company, Hershey, PA, USA

Correspondence: [*] Correspondence to: Giulio Maria Pasinetti, MD, PhD, Department of Neurology, The Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1137, New York, NY 10029, USA. Tel.: +1 212 241 7938; Fax: +1 212 876 9042; E-mail: giulio.pasinetti@mssm.edu.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder, characterized by pathological aggregates of amyloid peptide-β (Aβ) 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-β oligomerization to prevent synaptic deficits. Methods:We tested the effects of three different cocoa extracts, viz. Natural, Dutched, and Lavado extracts, on Aβ42 and Aβ40 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 Aβ. Results:Our results indicate that cocoa extracts are effective in preventing the oligomerization of Aβ, with Lavado extract being most effective. Lavado extract, but not Dutched extract, was effective in restoring the long term potentiation response reduced by oligomeric Aβ. 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.

Keywords: Amyloid, diet therapy, oligomerization, polyphenols, synapses

DOI: 10.3233/JAD-132231

Journal: Journal of Alzheimer's Disease, vol. 41, no. 2, pp. 643-650, 2014