Grape seed polyphenolic extract specifically decreases Aβ∗56 in the brains of Tg2576 mice

Amyloid- (A) oligomers, found in the brains of Alzheimer's disease (AD) patients and transgenic mouse models of AD, cause synaptotoxicity and memory impairment. Grape seed polyphenolic extract (GSPE) inhibits A oligomerization in vitro and attenuates cognitive impairment and AD-related neuropathology in the brains of transgenic mice. In the current study, GSPE was administered to Tg2576 mice for a period of five months. Treatment significantly decreased brain levels of A*56, a 56-kDa A oligomer previously shown to induce memory dysfunction in rodents, without changing the levels of transgenic amyloid- protein precursor, monomeric A, or other A oligomers. These results thus provide the first demonstration that a safe and affordable intervention can lower the levels of a memory-impairing A oligomer in vivo and strongly suggest that GSPE should be further tested as a potential prevention and/or therapy for AD.