Grape Derived Polyphenols Attenuate Tau Neuropathology in a Mouse Model of Alzheimer's Disease

• Published in: Journal of Alzheimer's disease Vol. 22; no. 2; pp. 653 - 661
• Main Authors: Wang, Jun, Santa-Maria, Ismael, Ho, Lap, Ksiezak-Reding, Hanna, Ono, Kenjiro, Teplow, David B., Pasinetti, Giulio Maria
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.01.2010
• Subjects: Alzheimer Disease - complications; Animals; Body Weight - drug effects; Disease Models, Animal; Flavonoids - therapeutic use; Humans; Mice; Microscopy, Electron, Transmission; Mutation - genetics; Neurofibrillary Tangles - pathology; Neurofibrillary Tangles - ultrastructure; Phenols - therapeutic use; Phytotherapy - methods; Polyphenols; Seeds - chemistry; Signal Transduction - drug effects; Spectrum Analysis; tau Proteins - genetics; tau Proteins - metabolism; Tauopathies - drug therapy; Tauopathies - etiology; Vitis; Aggregation; tauopathies; hyperphosphorylation; Alzheimer's disease; neurofibrillary tangles
• ISSN: 1387-2877; 1875-8908
• DOI: 10.3233/JAD-2010-101074

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.