Amelioration of early cognitive deficits by aged garlic extract in Alzheimer's transgenic mice

Subtle accumulation of beta-amyloid peptide (AP) oligomers of Ap 42 species in particular, is known to correlate with cognitive deficits independent of Ap plaque deposition in the brain. Majority of the research showing behavioral improvement after cerebral Ap reduction has been reported when the animals carried fewer/ abundant amyloid plaques in the brain. Very few studies have addressed whether or not behavioral deficits exist even at the pre-plaque stage or in the absence of plaques that would parallel the mild cognitive impairment (MCI) stage of Alzheimer's disease (AD). Current study was undertaken to determine whether there exists any cognitive impairment during the pre-plaque stage which may parallel the MCI stage of AD, and to confirm whether the observed behavioral deficits correlate with A beta 42 predominance. In addition, the study determined whether anti-amyloidogenic effects of dietary aged garlic extract would prevent progressive behavioral impairment. For this purpose we used Tg2576 model showing slow plaque development with a predominance of Ap 40, and the TgCRND8 model showing accelerated plaque development with a predominance of A beta 42. The results show that at 2 months of age Tg2576 mice did not exhibit behavioral impairment in any of the tasks studied. While 2-month-old TgCRND8 mice displayed only a subtle behavioral deficit that matched the behavioral deficits observed in 7-month-old Tg2576 mice which may correlate with the MCI stage of AD. TgCRND8 mice at 7 months of age exhibited advanced deterioration in all behavioral tasks studied, suggesting that accelerated Ap accumulation and the predominance of A beta 42 species may account for the pronounced cognitive deficits observed in TgCRND8. Feeding of aged garlic extract prevented deterioration of hippocampal based memory tasks in these mice, suggesting that aged garlic extract has a potential for preventing AD progression. Copyright 0 2007 John Wiley & Sons, Ltd.