Affiliations: [a] Department of Neurology and Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA | [b] Alzheimer Disease Research Unit, CIEN Foundation-Queen Sofia Foundation, Madrid, Spain | [c] Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA | [d] Kanazawa University Graduate School of Medical Science, Takara-Machi, Kanazawa, Japan | [e] Department of Neurology, David Geffen School of Medicine, and Brain Research Institute, and Molecular Biology Institute, University of California, Los Angeles, CA, USA
Correspondence:
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Correspondence to: Giulio Maria Pasinetti, Mount Sinai School of Medicine, Department of Neurology, One Gustave L. Levy Place, Box 1137, New York, NY 10029, USA. Tel.: +1 212 241 7938; Fax: +1 212 876 9042; E-mail: [email protected].
Note: [1] These authors contributed equally to this study.
Abstract: Aggregation of microtubule-associated protein tau into insoluble intracellular neurofibrillary tangles is a characteristic hallmark of Alzheimer's disease (AD) and other neurodegenerative diseases, including progressive supranuclear palsy, argyrophilic grain disease, corticobasal degeneration, frontotemporal dementias with Parkinsonism linked to chromosome 17, and Pick's disease. Tau is abnormally hyperphosphorylated in AD and aberrant tau phosphorylation contributes to the neuropathology of AD and other tauopathies. Anti-aggregation and anti-phosphorylation are main approaches for tau-based therapy. In this study, we report that a select grape-seed polyphenol extract (GSPE) could potently interfere with the assembly of tau peptides into neurotoxic aggregates. Moreover, oral administration of GSPE significantly attenuated the development of AD type tau neuropathology in the brain of TMHT mouse model of AD through mechanisms associated with attenuation of extracellular signal-receptor kinase 1/2 signaling in the brain.
